Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • 2020-2024
  • 1995-1999
  • 1990-1994  (850)
  • 1965-1969  (59)
  • 1930-1934
  • 1900-1904
  • 1870-1879
  • 1850-1859
  • 1810-1819
  • 2020
  • 1990  (850)
  • 1965  (59)
  • 1931
  • 1893
  • 1879
  • 1817
  • 1810
  • Biochemistry and Biotechnology  (784)
  • pharmacokinetics  (125)
Source
Material
Years
  • 2020-2024
  • 1995-1999
  • 1990-1994  (850)
  • 1965-1969  (59)
  • 1930-1934
    • +
Year
Keywords
  • 101
    Electronic Resource
    Electronic Resource
    Model for the interaction of amphiphilic helices with troponin C and calmodulin (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 234-248 
    Details
    ISSN: 0887-3585
    Keywords: computer modelling ; Ca2+-binding proteins ; hydrophobic binding interactions ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Crystals of troponin are stabilized by an intermolecular interaction that involves the packing of helix A from the N-terminal domain of one molecule onto the exposed hydrophobic cleft of the C-terminal domain of a symmetry related molecules. Analysis of this molecular recognition interaction in troponin C suggests a possible mode for the binding of amphiphilic helical molecules to troponin C and to calmodulin. From the template provided by this troponin C packing, it has been possible to build a model of the contact region of mastoporan as it might be bound to the two Ca2+ binding proteins. A possible binding mode of melittin to calmodulin is also proposed. Although some of the characteristics of binding are similar for the two amphiphilic peptides, the increased length of melittin requires a significant bend in the calmodulin central helix similar to that suggested recently for the myosin light chain kinase calmodulin binding peptide (Persechini and Kretsinger: Journal of Cardiovascular Pharmacology 12:501-512, 1988). Not only are the hydrophobic interactions important in this model, but there are several favorable electrostatic interactions that are predicted as a result of the molecular modeling. The regions of troponin-C and calmodulin to which amphiphilic helices bind are similar to the regions to which the neuroleptic drugs such as trifluoperazine have been predicted to bind (Strynadka and James: Proteins 3:1-17, 1988).
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070305
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 102
    Electronic Resource
    Electronic Resource
    The design of idealized α/β-barrels: Analysis of β-sheet closure requirements (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 249-256 
    Details
    ISSN: 0887-3585
    Keywords: β-barrels ; β-strand ; scaffold design ; molecular modeling ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The 8-old parallel α/β-barrel topology is encountered in proteins that display an impressive variety of functions, suggesting that this topology may be a rather nonspecific and stable folding motif. Consequently, this motif can be considered as an interesting framework to design novel proteins. It has been shown that the shape of the β-sheet portion of the barrel can be approximated by a hyperboloid. This geometric object may therefore be used as a scaffold to construct an idealized eight-standard β-barrel. To facilitate the de novo design of such structures, a collection of modelling tools has been developed allowing secondary structure elements to be mapped onto the scaffold surface and rotation and translation operations to be performed about user defined axes while evaluating their contribution to the conformational energy of the system. These tools have been applied in a systematic study assessing the φ, ψ requirements to design symmetric eight standard β barrels with optimal hydrogen bonding between adjacent β-strands. It is observed that: (a) the β-sheet structure can be closed without introducing irregular stagger between β-strands and (b) the region of φ, ψ dihedral angle space compatible with the formation of regular symmetric eight standard β-barrels coincides with the φ, ψ region corresponding to average β-strands in known protein structures, suggesting that barrel closure does not impose gross constraints on β-strand geometry.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070306
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 103
    Electronic Resource
    Electronic Resource
    The characterization of recombinant mouse glandular kallikreins from E. coli (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 280-290 
    Details
    ISSN: 0887-3585
    Keywords: proteases ; protein turnover ; post-translational processing ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A system has been developed or the expression in E. coli of 12 of the 14 expressed mouse submandibular gland kallikreins as cassettes subcloned directly from cDNA. Using the epidermal growth factor binding protein (mGK-9) and the γ-subunit of nerve growth factor (nGK)-3, as test cases, mature processed forms, obtained as functionally active proteins, as well as various precursor forms, were isolated. The expression system described allows rapid isolation of kallikrein protein from corresponding cDNA with yields of approximately 1.0 mg of purified protein from 10 g of initial cell paste. This expression system will facilitate structure/function studies of the mouse glandular kallikrein gene family and help elucidate the regions of the mature proteins responsible for the diverse catalytic behavior and growth factors interactions observed in this family of proteins.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070309
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 104
    Electronic Resource
    Electronic Resource
    HERA - A program to draw schematic diagrams of protein secondary structures (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 203-212 
    Details
    ISSN: 0887-3585
    Keywords: hydrogen bonding diagram ; motifs ; helical wheel ; helical net ; protein structure ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A program is described which generates hydrogen bonding diagrams of protein structures and optionally helical wheels and helical nets. The program can also be used simply to calculate the connectivities of β-strands and to automatically extract simple structural motifs such as hairpins or Greek keys. The program greatly reduces the effort required to produce these diagrams and offers considerable flexibility in the information which can be represented. The usefulness of the program is illustrated by several examples including comparing homologous families, correlating protein structure with attributes of individual residues, and extracting all examples of the ψ-loop motif from the Brookhaven Data Bank.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080303
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 105
    Electronic Resource
    Electronic Resource
    Structural homology among the peroxidase enzyme family revealed by hydrophobic cluster analysis (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 251-257 
    Details
    ISSN: 0887-3585
    Keywords: peroxidase ; active site ; structure conservation ; hydrophobic cluster analysis ; sequence comparison ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A number of peroxidase amino acid sequences show limited homology to short regions comprising the known active site cleft of yeast cytochrome c peroxidase. Otherwise no clear homology is visible in linear alignments between this enzyme and other peroxidases. We have subjected eight peroxidase sequences to hydrophobic cluster analysis. Our results suggest that these peroxidases are evolutionary related and that they share many folding characteristics.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080307
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 106
    Electronic Resource
    Electronic Resource
    Identification of protein folds: Matching hydrophobicity patterns of sequence sets with solvent accessibility patterns of known structures (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 257-264 
    Details
    ISSN: 0887-3585
    Keywords: protein families ; structure prediction ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Hydrophobic side chains often are buried in the interior of a protein, and evolutionarily related proteins usually maintain the hydrophobic character of buried position. In this paper we shown that a pattern of hydrophobicity values derived from a set of related protein sequences is well correlated with the linear pattern of side-chain solvent accessibility values, calculated from a known protein structure representative of the sequences. In several cases, information from aligned sequences can be used to select the correct tertiary fold from a large database of protein structures.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070307
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 107
    Electronic Resource
    Electronic Resource
    ALMA, an editor for large sequence alignments (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 291-295 
    Details
    ISSN: 0887-3585
    Keywords: full screen editor ; consensus calculation ; secondary structure ; automatic alignment ; alignment merging ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A dedicated sequence editor ALMA, was developed for aligning many sequences of proteins or RNA molecules or longer DNA fragments. Like previously published editors, ALMA is menu directed, screen oriented, and offers similarity and consensus display. ALMA has the additional features of collective movement of sequences, acceptance of input from many sources including structure files and databases, secondary structure display, and easy merging of alignments. In order to maintain sequence integrity and save disk space, gaps and sequences are stored separately. Automatic recovery of a session is possible. Finally, The program allows interaction between manual and automatic alignment.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070310
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 108
    Electronic Resource
    Electronic Resource
    Comparative modeling methods: Application to the family of the mammalian serine proteases (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 317-334 
    Details
    ISSN: 0887-3585
    Keywords: protein structure ; computer modeling ; structure prediction ; sequence homology ; structure homology ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Comparative modeling methods are described that can be used to construct a three-dimensional model structure of a new protein from knowledge of its sequence and of the experimental structure and sequences of other members of its homology family. The methods are illustrated with the mammalian serine protease family, for which seven experimental structures have been reported in the literature, and the sequence for over 35 different protein members of the family are available. The strategy for modeling these proteins is presented, and criteria are developed for determining and assigning the reliability of the modeled structure. Criteria are described that are specially designed to help detect cases in which it is likely that the local structure diverges significantly from the usual conformation of the family.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070404
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 109
    Electronic Resource
    Electronic Resource
    The building of protein structures form α-carbon coordinates (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 366-377 
    Details
    ISSN: 0887-3585
    Keywords: computer modeling ; protein ; structure ; α-carbons ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A procedure for the construction of complete protein structures from only αcarbon coordinates is described. This involves building the backbone by sequential addition of Pro, Gly, or Ala residues. This main chain structure is then refined using molecular dynamics. Side chains are constructed by sequential addition of atoms with intermediate molecular dynamics refinement. For α lytic protease (a structure that is mostly β sheet) a backbone root mean square deviation (RMSD) of 0.19 Å and an overall RMSD of 1.24 Å from the crystallographic coordinates are attained. For troponin C (67% β-helix), where the coordinates are available only for the α-carbons, a backbone RMSD of 0.41 Å and an overall RMSD of 1.68 Å are attained (fits kindly provided by Dr. Michael James and Natalie Strynadka). For flavodoxin a backbone RMSD of 0.49 Å and an overall RMSD of 1.64 Å were attained.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070408
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 110
    Electronic Resource
    Electronic Resource
    Quantitative organization of the known protein x-ray structures. I. Methods and short-length-scale results (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 378-402 
    Details
    ISSN: 0887-3585
    Keywords: conformational distance ; conformational comparison ; generalized bond matrix representation ; structure space ; evolution ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We address herein the problem of delineating the relationships between the known protein structures. In order to study this problem, methods have been developed to represent arbitrarily sized fragments of biopolymer backbone, and to compare distributions of such fragments. These methods are applied to a classification of 123 structures representing the entire set of known x-ray structures. The resulting data are analyzed (on the four-Cα length scale) to determine both the large-scale organization of the set of known structures (i.e., the relationships between large groups of structures, each comprised of proteins that are structurally related) and its local structure (i.e., the quantitative degree of similarity between any two specific structures). It is shown that the set of structures from a continuum of structural types, ranging from allhelical to all-sheet/barrel proteins. It is further demonstrated that the density of protein structures is not uniform across this continuum, but rather that structures cluster in certain regions, separated by regions of lower population. The properties of the various regions of the structural space are determined. The existence is demonstrated of strong quantitative correlations between the contents of different types of four-Cα fragments within protein structures, which imply significant constraints on the types of architecture that can occur in proteins. Analysis of the distribution of structures demonstrates some hitherto unsuspected similarities and suggests that, in some circumstances, neither structural similarity no sequence homology may be necessary conditions for evolutionary relationship between proteins. It is also suggested that these unsuspected similarities may imply similar folding mechanisms for structures of apparently different global architecture. Cases are also noted in which apparently similar structures may fold by different mechanisms. The connection between structure and dynamic properties is discussed, and a possible role of dynamics in the evolution of protein structures is suggested. The sensitivity of the methods presented herein to anomalies of structure refinement is demonstrated. It is suggested that present results provide a frame-work for analyzing experimental results on structural similarity obtained using vibrational circular dichroism spectra, which are sensitive to local backbone structure.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070409
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 111
    Electronic Resource
    Electronic Resource
    Distinct character in hydrophobicity of amino acid compositions of mitochondrial proteins (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 173-178 
    Details
    ISSN: 0887-3585
    Keywords: mitochondria ; amino acid composition ; hydrophobicity ; composition space ; membrane protein ; transmembrane region ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A compact mitochondrial gene contains all essential information about the synthesis of mitochondrial proteins which play their roles in a small compartment of the mitochondrium. Almost no noncoding regions have been found through the gene, but a necessary set of tRNAs for the 20 amino acids is provided for biosynthesis, some of them coding different amino acids from those in a usual cell. Since the gene is so compact that the produced proteins would have some characteristic aspects for the mitrochondrium, amino acid compositions of mitochondrial proteins (mt-proteins) were examined in the 20-dimensional composition space. The results show that compositions of proteins translated from the mitochondrial genes have a distinct character having more hydrophobic content than others, which is illustrated by a clustered distribution in the multidimensional composition space. The cluster is located at the tail edge of the global distribution pattern of a Gaussian shape for other various kinds of proteins in the space. The mt-proteins are rich in hydrophobic amino acids as is a membrane protein, but are different from other membrane proteins in a lesser content of Val. A good correlation found between the base and amino acid compositions for the mitochondria was examined in comparison to those of organisms such as thermophilic bacterium having an extreme G-C-rich base composition.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080207
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 112
    Electronic Resource
    Electronic Resource
    Models of δ-hemolysin membrane channels and crystal structures (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 213-225 
    Details
    ISSN: 0887-3585
    Keywords: molecular modeling ; energy calculations ; δ-hemolysin ; melittin ; crystal packing ; raft ; bilayer ; membrane insertion ; channel formation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Molecular modeling and energy calculations have been used to study how δ-hemolysin and melittin helices may aggregate on membrane surfaces and insert through membranes to form channels. In these models adjacent antiparallel amphipathic helices form planar “raft” structures, in which one surface is hydrophobic and the other hydrophilic. Models of δ-hemolysin crystal structure were developed using these “rafts.” These models are based on the unit cell constants and the crystal symmetry obtained from the preliminary crystal data. Energy calculations favor channel models of δ-hemolysin with six or eight monomers per channel.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080304
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 113
    Electronic Resource
    Electronic Resource
    Changes in secondary structure follow the dissociation of human insulin hexamers: A circular dichroism study (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 280-286 
    Details
    ISSN: 0887-3585
    Keywords: circular dichroism ; secondary structure ; insulin ; insulin analogs ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Vacuum UV circular dichroism spectra measured down to 178 nm for hexameric 2-zinc human insulin, zinc-free human insulin, and the two engineered and biologically active monomeric mutants, [B/S9D] and [BS9D, T27E] human insulin, show significant differences. The secondary structure analysis of the 2-zinc human insulin (T6) in neutral solution was determined: 57% helix, 1% β-strand, 18% turn, and 24% random coil. This is very close to the corresponding crystal structure showing that the solution and solid structures are similar. The secondary structure of the monomer shows a 10-15% increase in antiparallel β-structure and a corresponding reduction in random coil structure. These structural changes are consistent with an independent analysis of the corresponding difference spectra. The advantage of secondary structure analyses of difference spectra is that the contribution of odd spectral features stemming mainly from side chain chromophores is minimized and the sensitivity of the analyses improved. Analysis of the CD spectra of T6 2-zinc, zinc-free human insulin and monomeric mutant insulin by singular value decomposition indicates that the secondary structure changes following the dissociation of hexamers into dimers and monomers are two-state processes.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080309
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 114
    Electronic Resource
    Electronic Resource
    A helix-turn-strand structural motif common in α-β proteins (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 334-340 
    Details
    ISSN: 0887-3585
    Keywords: protein structure ; structural comparison ; α-β barrels ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: By exhaustive structural comparisons, we have found that about one-third of the α-helix-turn-β-strand polypeptides in α-β barrel domains share a common structural motif. The chief characteristics of this motif are that first, the geometry of the turn between the α-helix and the β-strand is somewhat constrained, and second, the β-strand contains a hydrophobic patch that fits into a hydrophobic pocket on the α-helix. The geometry of the turn does not seem to be a major determinant of the α-β unit, because the turns vary in length from four to six residues. However, the motif does not occur when there are few constraints on the geometry of the turn-for instance, when the turns between the α-helix and the β-strands are very long. It also occurs much less frequently in flat-sheet α-β proteins, where the topology is much less regular and the amount of twist on the sheet varies considerably more than in the barrel proteins. The motif may be one of the basic building blocks from which α-β barrels are constructed.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080407
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 115
    Electronic Resource
    Electronic Resource
    Fragment peptide library for classification and functional prediction of proteins (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 341-351 
    Details
    ISSN: 0887-3585
    Keywords: conserved sequence ; diagnostic peptide ; superfamily classificaiton ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: From protein sequence comparison data found in the literature, a library was organized using peptide fragment sequences which are common to related proteins. Each of the fragments was then examined for its occurrence in all the protein superfamilies defined by the NBRF-PIR data base. We have selected those fragment peptides that appear exclusively in one or a few superfamilies, and thus made a library of fragment peptides that characterize specific superfamilies. Such characteristic peptides are, in general, five to seven residues long and contain unusually high proportions of glycine and cysteine. This collection is a useful resource for the classification and functional prediction of protein molecules.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080408
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 116
    Electronic Resource
    Electronic Resource
    The structure of rubredoxin from Desulfovibrio desulfuricans strain 27774 at 1.5 Å resolution (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 352-364 
    Details
    ISSN: 0887-3585
    Keywords: crystallography ; refinement ; structure comparison ; molecular replacement ; precision ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The structure of a small rubredoxin from the bacterium Desulfovibrio desulfuricans has been determined and refined at 1.5 Å resolution. The hairpin loop containing seven residues in other rubredoxins is missing in this 45 residue molecule, and once that fact was determined by amino acid sequencing studies, refinement progressed smoothly to an R value of 0.093 for all reflections from 5 to 1.5 Å resolution. Nearly all of the water molecules in the well-ordered triclinic unit cell have been added to the crystallographic model. As in the other refined rubredoxin models, the Fe-S4 complex is slightly distorted from ideal tetrahedral coordination.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080409
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 117
    Electronic Resource
    Electronic Resource
    α-Helical coiled coils and bundles: How to design an α-helical protein (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 1-15 
    Details
    ISSN: 0887-3585
    Keywords: α-fibrous proteins ; 4-α-helix bundle ; membrane-spanning proteins ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070102
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 118
    Electronic Resource
    Electronic Resource
    Protein-drug interactions: Characterization of inhibitor binding in complexes of DHFR with trimethoprim and related derivatives (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 52-61 
    Details
    ISSN: 0887-3585
    Keywords: molecular dynamics ; protein simulations ; dihydrofolate reductase ; trimethoprim ; drug binding ; solvation ; binding free energies ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Structural and thermodynamic interactions for the binding of trimethoprim and related congeners to the binary complex of diphydrofolate reductase (from chicken) and NADPH are explored using free energy simulation methods. Good agreement between structures from experimental X-ray refinement and molecular dynamics simulations is found for the complexes. Agreement with thermodyanmic measurements is found as well. Our thermodynamic calculations suggest that entropic contributions and desolvation thermodynamics can play a crucial role in overall bindings, and that extreme care must be taken in the use of simple model building to rationalize or predict protein-drug binding.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070106
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 119
    Electronic Resource
    Electronic Resource
    Evaluation of homology modeling of HIV Protease (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 172-184 
    Details
    ISSN: 0887-3585
    Keywords: aspartic proteases ; retroviral proteases ; sequence homology ; related structures ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The model of human immuno-deficiency virus (HIV-1) protease which was based on the crystal structure of Rous sarcoma virus (RSV) protease has been compared to the recently determined crystal structure of chemically synthesized HIV-1 protease. The overall difference between the model and crystal structure was 1.4 Å root mean square (rms) deviation for 86 superimposed Cα atoms. The position of the flexible flap differs in the model and six residues at the amino terminus were incorrectly placed. With these exceptions, all atoms of the model and crystal structure agree to 2.11 Å runs deviation. The conformation of some surface bends in the model agrees less well with the crystal structure. Identical amino acids in RSV and HIV proteases were modeled more reliably than different types of amino acids. The amino acids which form the substrate binding site were modeled most accurately to 1.2 Å rms deviation for all atoms compared to the crystal structure. This suggests that functionally significant regions of related proteins can be modeled with high accuracy. The model gave correct predictions for residues making interactions with the substrate, and thereof could be used to design inhibitors, The model based on the RSV protease structure is more similar to the experimental structure than are previous models based on the structures of non-viral aspartic proteases.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070206
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 120
    Electronic Resource
    Electronic Resource
    Polyproline, β-turn helices. Novel secondary structures proposed for the tandem repeats within rhodopsin, synaptophysin, synexin, gliadin, RNA polymerase II, hordein, and gluten (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 125-155 
    Details
    ISSN: 0887-3585
    Keywords: phosphorylation ; tyrosine ; cis-peptide ; exocytosis ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Seven proteins each contain 8 to 52 tandem repeats of a unique class of oligopeptide. The consensus peptide for each is rhodopsin Tyr Pro Pro Gln Glysynapto-physin Tyr Gly Pro Gln Glysynexin Tyr Pro Pro Pro Pro Glygliadin Tyr Pro Pro Pro Gln ProRNA polymerase II Tyr Ser Pro Thr Ser Pro Serhordein Phe Pro Gln Gln Pro Gln Gln Progluten Tyr Pro Thr Ser Pro Gln Gn Gly TyrAlthough there is obvious variations of sequence and of length, the penta-to nonapeptides share an initial Tyr(or Phe) and have high Pro contents and abundant Gly, Gln, and Ser. We have evaluated helical models that both recognize the uniqueness of these sequence repeats and accommodate variations on the basic theme.We have developed a group of related heical model for these proteins with about three oligopeptide repeats per turn of 10-20 Å. These models share several common features: Most of the φ dihedral angels are -54°, to accommodate Pro at all positions expect the first (Tyr). Except for the β-turns, most ψ dihedral angles are near +140° as found in polyproline. Each oligopeptide has at least one β-turn; several have two. Some contains a cis-Tyr, Pro peptide bond; a few have a cis-bond plus one β-turn. Tyr side chains vary from totally exposed to buried within the helices and could mode to accommodate either external hydrophobic interactions or phosphorylation. The several related structures seem to be readily interconverted without major change in the overall helical parameters, and therein may lie the key to their functions.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070204
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 121
    Electronic Resource
    Electronic Resource
    β-Lactamase of Bacillus licheniformis 749/C at 2 Å resolution (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 156-171 
    Details
    ISSN: 0887-3585
    Keywords: β-lactamase ; penicillinase ; penicillin-binding protein ; penicillin antibiotics ; X-ray diffraction ; protein structure prediction ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Two crystal (A and B) of the 29,500 Da Class A β-lactamase (penicillinase) from Bacillus licheniformis 749/C have been examined crystallographically. The structure of B-form crystals has been solved to 2 Å resolution, the starting model for which was a 3.5 Å structure obtained from A-form crystals. The β-lactamase has an α + β structure with 11 helices and 5 β-strands seen also in a peinicilin target DD-peptidase of Streptomyces R61.1 Atomic parameters of the two molecules in the asymmetric unit were refined by simulated annealing at 2.0 Å resolution. The R factor is 0.208 for the 27,330 data greater than 3 (F), with water molecules excluded from the model. The catalytic Ser-70 is at the N-terminus of a helix and is within hydrogen bonding distance of conversed Lys-73. Also interacting with the Lys-73 are Asn-132 and the conserved Glu-166, which is on a potentially flexible helix-containing loop. The structure suggests the binding of β-lactam substrates is facilitated by interactions with Lys-234, Tyhr-235, and Ala-237 in a conserved β-strand peptide, which is antiparallel to the β-lactam's acylamido linkage; an exposed cavity near Asn-170 exits for acylamido Substituent. The reactive double bond of clavulanate-type inhibitors may interact with Arg-244 on the fourth β-strand. A very similar binding site architecture is seen in the DD-peptidase.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070205
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 122
    Electronic Resource
    Electronic Resource
    A mutant T4 lysozyme (Val 131 → Ala) designed to increase thermostability by the reduction of strain within an α-helix (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 198-204 
    Details
    ISSN: 0887-3585
    Keywords: protein stability ; protein design ; strain ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: An attempt has been made to identify residues in T4 phage lyoszyme that may have strained conformations and, by appropriate site-directed replacements, to reduce this strain and thus increase the thermostability of the protein. Valine 131, within α-helix 126-134, was identified as a potential candidate. Its side-chain rotational as a potential candidate. Its side-chain rotation angle, χ1, differs by approximately 18° from the low-energy trans configuration. In addition, it is largely solvent exposed, yet is held in a rigid conformation. The mutant protein with Val 131 replaced by alanine temperature 0.9°C higher than that of wildtype lyoszyme at pH 2.8. As a control, The mutant Val 131 → Thr was also constructed and its melting temperature was found to be marginally lower than wild type. Higher-resolution crystal structure determination of the mutant lysozymes show that their structure are virtually identical with that of wild-type lyoszyme, except for the Val → Ala or Val → Thr replacement. Analysis of the different structures suggests that the design of the Val→Ala substitution was, in principle, successful, although the apparent gain in stability caused by reduction in strain is modest and is somewhat offset by the loss of hydrophobic interactions and by entrophic effects. The results also help to provide a structural retionalization that alanine has a higher helix propensity than valine or theronine.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070208
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 123
    Electronic Resource
    Electronic Resource
    Molecular dynamics study of secondary structure motion in proteins: Application to myohemerythrin (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 265-279 
    Details
    ISSN: 0887-3585
    Keywords: potential of means force ; motions of helices ; correlated fluctuations ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The concept of secondary structure motions is examined in a molecular dynamics simulation of the protein myohemerythrin. We extracted from the simulation a corresponding trajectory of helices and demonstrated that the fluctuations of the protein are dominated by a rigid shift of these secondary structure elements. The relative motions of the helices are regular, with no clear periodicity. They are bounded by ∼2 for the center of mass motions and by 20° for the relative orientations. The potential of mean force for the interactions of the helices was calculated, and the correlations between the different extended motions were investigated. It shown that the one-dimensional mean force potentials are close to quadratic for most of the helices coordinates. The anharmonicity is reflected by changes in the direction of the normal modes as a function of the energy and by the existence of multiple free energy minima for the helices packing. The multiple conformations are associated with a single type of secondary structure coordinate: the angle that describes the relative orientation of the helices in a plane perpendicular to the line connecting their center of mass.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070308
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 124
    Electronic Resource
    Electronic Resource
    Accommodation of single amino acid insertions by the native state of staphylococcal nuclease (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 299-305 
    Details
    ISSN: 0887-3585
    Keywords: protein stability ; guanidine hydrochloride denaturation ; conformational changes ; polypeptide backbone ; alanine insertion ; glycine insertion ; circular dichroism spectra ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Single alanine and glycine insertions were introduced at 20 randomly selected positions in staphylococcal nuclease. The resulting changes in catalytic activity and in stability to guanidine hydrochloride denaturation indicate that the native state structure is frequently able to accommodate the extra residue without great difficulty, even insertions within secondary structural elements such as alpha helices and beta sheets. On average, an inserted residue reduces the free energy of denaturation (ΔGH2O) by an amount roughly comparable to an alanine or glycine substitution for one of the residues flanking the site of insertion. Several positions outside of the enzyme active site were found where insertions, but not substitutions, lead to structural changes that modify catalytic activity and the circular dichroism spectrum. Amino acid insertions represent a virtually unexplored class of genetic mutation that may prove complementary to amino acid substitutions for engineering proteins with altered functional and structural properties.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070402
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 125
    Electronic Resource
    Electronic Resource
    Crystal structure of myoglobin form a synthetic gene (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 358-365 
    Details
    ISSN: 0887-3585
    Keywords: synthetic myoglobins ; X-ray crystallography ; protein engineering ; heme proteins ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Crystal have been grown of myoglobin produced in Escherichia coli from a synthetic gene, and the structure has been solved to 1.9 Å resolution. The space group of the crystals is P6, which is different from previously solved myoglobin crystal forms. The synthetic myoglobin is essentially identical to myoglobin isolated from sperm whale tissue, except for the retention of the initiator methionine at the N-terminus and the substitution of asparagine for aspartic acid at position 122. Superposition of the coordinates of native and synthetic sperm whale myoglobins reveals only minor changes in the positions of main chain atoms and roeientation of some surface side chains. Crystals of variant of the “synthetic” myoglobin have also been grown for structural analysis of the role of key amino acid residues in ligand and specificity.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070407
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 126
    Electronic Resource
    Electronic Resource
    Announcement (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. i 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080102
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 127
    Electronic Resource
    Electronic Resource
    Energetics of the structure and chain tilting of antiparallel β-barrels in proteins (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 14-22 
    Details
    ISSN: 0887-3585
    Keywords: computation ; conformational energy ; interactions in proteins ; protein folding ; twisted β-sheets ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The preferred structural pattern of antiparallel β-barrels in proteins, described as the right-handed tilting of the peptide strands with respect to the axis of the barrel, is accounted for in terms of intra- and interchain interaction energies. It is related to the preference of β-sheets for right-handed twisting. Conformational energy computations have been carried out on three eight-stranded antiparallel β-barrels composed of six-residue strands, in which L-Val and Gly alternate, and having a right-handed, a left-handed, or no tilt. After energy minimization, the relative energies of these structures were 0.0, 8.6, and 46.1 kcal/mol, respectively; i.e., the right-tilted β-barrel is favored energetically, in agreement with anti-parallel β-barrels observed in proteins. Tilting of the barrel is favored, relative to the nontilted structure, by both intra- and interstrand interactions, because tilting allows better packing of the bulky side chains. On the other hand, the energy difference between the left- and right-tilted barrels arises essentially from intrachain interactions. This is a consequence of the preference of β-sheets for a right-handed twist. Space limitations inside the barrel are satisfied if there is an alternation of bulky residues and residues with small or no side chain (preferably Gly) in neighboring positions on adjacent strands. Such a pattern is seen frequently in antiparallel β-barrels of globular proteins. The computations indicate that a structure with Val…Gly pairs can be accommodated in a β-barrel with no distortion.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080105
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 128
    Electronic Resource
    Electronic Resource
    Masthead (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990) 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080201
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 129
    Electronic Resource
    Electronic Resource
    Comparison of the structures of globins and phycocyanins: Evidence for evolutionary relationship (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 133-155 
    Details
    ISSN: 0887-3585
    Keywords: evolution ; alignment ; globins ; phycocyanin ; helix interfaces ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Globins and phycocyanins are two classes of proteins with different function, different ligands, and no substantial sequence similarity, yet the conformations of their polypeptide chains show very similar folding patterns. Does this arise from a genuine, albeit very distant, evolutionary relationship, or does it represent a common solution of a structural problem? We address this question by a very detailed comparison of the structures of the two protein families. An analysis of the helices and their interactions shows many features common to globins and phycocyanins, including some exceptional features of the globins such as a 3-10 C helix and the unusual “crossed-ridge” packing pattern at the B/E helix interfaces. We conclude that the evidence supports the hypothesis of distant evolutionary relationship between globins and phycocyanins.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080204
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 130
    Electronic Resource
    Electronic Resource
    An expectation maximization (EM) algorithm for the identification and characterization of common sites in unaligned biopolymer sequences (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 41-51 
    Details
    ISSN: 0887-3585
    Keywords: DNA binding proteins ; maximum likelihood ; CRP ; finite mixtures ; transcription regulation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Statistical methodology for the identification and characterization of protein binding sites in a set of unaligned DNA fragments is presented. Each sequence must contain at least one common site. No alignment of the sites is required. Instead, the uncertainty in the location of the sites is handled by employing the missing information principle to develop an “expectation maximization” (EM) algorithm. This approach allows for the simultaneous identification of the sites and characterization of the binding motifs. The reliability of the algorithm increases with the number of fragments, but the computations increase only linearly. The method is illustrated with an example, using known cyclic adenosine monophophate receptor protein (CRP) binding sites. The final motif is utilized in a search for undiscovered CRP binding sites.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070105
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 131
    Electronic Resource
    Electronic Resource
    Understanding structural relationships proteins of unsolved three-dimensional structure (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 99-111 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070202
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 132
    Electronic Resource
    Electronic Resource
    Protein secondary structure and circular dichroism: A practical guide (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 205-214 
    Details
    ISSN: 0887-3585
    Keywords: protein secondary structures ; circular dichroism ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070302
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 133
    Electronic Resource
    Electronic Resource
    Modelling of the human intercellular adhesion molecule-1, the human rhinovirus major group receptor (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 227-233 
    Details
    ISSN: 0887-3585
    Keywords: rhinovirus receptor ; ICAM-1 ; structure prediction ; immunoglobulin superfamily ; docking receptor to virus ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A model has been built of the amino-terminal domain of the intercellular adhesion molecule-1 (ICAM-1), the receptor for most human rhinovirus serotypes. The model was based on sequence and presumed structural homology to immunoglobulin constant domains. It fits well into the putative receptors attachment site, the canyon, on the human rhinovirus-14 (HRV14) surface in a manner consistent with most of the mutational data for ICMA-1 (Staunton, D. E., Dustin, M. L., Erickson, H. P., Springer, T. A. Cell, in press, 1989) and HRV14 (Colonno, R. J., Condra, J. H., Mizutani, S., Callahan, P. L., Davies, M. E., Murcko, M. A. Proc. Natl. Acad. Sci. U.S.A. 85: 5449-5453, 1988).
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070304
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 134
    Electronic Resource
    Electronic Resource
    Prediction of homologous protein structures based on conformational searches and energetics (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 30-43 
    Details
    ISSN: 0887-3585
    Keywords: molecular mechanics ; solvation energy ; trypsin ; energy minimization ; side chains ; protein crystallography ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A “knowledge-based” method of predicting the unknown structure of a protein from a homologous known structure using energetics to determine a sidechain conformation is proposed. The method consists of exchangin the residues in the known structure for the sequence of the unknown protein. Then a conformational search with molecular mechanics energy minimization is done on the exchanged residues. The lowest energy conformer is the one picked to be the predicted structure. In the structure of bovine trypsin, the importance of including a solvation energy term in the search is demonstrated for solvent accessible residues, while molecular mechanics alone is enough to correctly predict the conformation of internal residues. The correctness of the model is assessed by a volume error overlap of the predicted structure compared to the crystal structure. Finally, the structure of rat trypsin is predicted from the crystal structure of bovine trypsin. The sequences of these two proteins are 74% identical and all of the significant changes between them are on external residues. Thus, the inclusion of solvation energy in the conformational search is necessary to accurately predict the structure of the exchanged residues.
    Additional Material: 13 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080107
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 135
    Electronic Resource
    Electronic Resource
    Modeling of agonist binding to the ligand-gated ion channel superfamily of receptors (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 386-397 
    Details
    ISSN: 0887-3585
    Keywords: LGIC superfamily ; proto-binding site ; cys-loop motif ; docking model ; anionic site ; specificity residue ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A generalized model is presented of agonist binding to ligand-gated ion channels (LGICs). Broad similarity in the structure of agonists suggests that the binding sites of LGICs may have evolved from a protobinding site. Aligned sequence data identified as a candidate for such a site a highly conserved 15 residue stretch of primary structure in the N-terminal extracellular region of all known LGIC subunits. We modeled this subregion, termed the cys-loop, as a rigid, amphiphilic β-hairpin and propose that it may form a major determinant of a conserved structural binding cleft.In the model of the binding complex (1) an invariant aspartate residue at position 11 of the cys-loop is the anionic site interacting with the positively charged amine group of agonists, (2) a local dipole within the π-electron system of agonists is favorably oriented in the electrostatic field of the invariant aspartate, (3) the ε ring-proton of a conserved aromatic residue at the turn of the cys-loop interacts orthogonally with the agonist α-electron density at its electronegative center, and (4) selective recognition is partly a result of the type of amino acid residue at position 6 of the cys-loop. Additionally, the formation of a hydrogen bond between the electronegative atom of the π-electron system of agonist and a complementary group in the receptor may be important in the high-affinity binding of agonists.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080412
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 136
    Electronic Resource
    Electronic Resource
    Design of biologically active, conformationally constrained GnRH antagonists (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 295-304 
    Details
    ISSN: 0887-3585
    Keywords: gonadotropin-releasing hormone ; molecular dynamics ; nuclear magnetic resonance ; antagonist design ; conformation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The introduction of conformational constraints into a flexible peptide hormone can be exploited to develop models for the conformation required for receptor binding and activity. In this review, we illustrate this approach to analog design using our work on antagonists of gonadotropin-releasing hormone (GnRH). Design of a conformationally constrained, competitive antagonist of GnRH, cyclo[Δ3,4 Pro-D4ClPhe-DTrp-Ser-Tyr-DTrp-NMeLeu-Arg-Pro-βAla], led to the prediction of its bioactive conformation. Template forcing experiments show that this conformation is accessible to other active GnRH analogs. Two-dimensional NMR studies verified the predicted conformation in solution. The predicted binding conformation has recently been used to design two new analogs incorporating side chain-side chain linkages suggested by the conformational model: These analogs were synthesized and the one predicted to be most similar to the parent conformation had equivalent potency while the second, designed to refine the conformational hypothesis, was found to exhibit enhanced potency, thus confirming the original binding conformation hypothesis. These compounds and their derivatives now provide a new class of GnRH antagonists possessing both high biological potency and limited conformational flexibility, thus making them ideal for both biophysical and structure-activity studies.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080403
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 137
    Electronic Resource
    Electronic Resource
    Automated docking of substrates to proteins by simulated annealing (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 195-202 
    Details
    ISSN: 0887-3585
    Keywords: simulated annealing ; computer-aided drug design ; substrate docking ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The Metropolis technique of conformation searching is combined with rapid energy evaluation using molecular affinity potentials to give an efficient procedure for docking substrates to macromolecules of known structure. The procedure works well on a number of crystallographic test systems, functionally reproducing the observed binding modes of several substrates.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080302
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 138
    Electronic Resource
    Electronic Resource
    Bundles of amphipathic transmembrane α-helices as a structural motif for ion-conducting channel proteins: Studies on sodium channels and acetylcholine receptors (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 226-236 
    Details
    ISSN: 0887-3585
    Keywords: protein structure ; ionic pores ; neural membranes ; protein design ; energy minimization ; molecular dynamics ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Channel proteins are transmembrane symmetric (or pseudosymmetric) oligomers organized around a central ionic pore. We present here a molecular model of the pore forming structures of two channel proteins with different primary structures and oligomeric size: the voltage-sensitive sodium channel and the nicotinic cholinergic receptor. We report low-energy arrangements of α-helical bundles calculated by semiempiricial potential energy functions and optimization routines and further refined using molecular dynamics. The ion-conducting pore is considered to be a symmetric or pseudosymmetric homooligomer of 3-5 amphipathic α-helices arranged such that the polar residues line a central hydrophilic pathway and the apolar residues face the hydrophobic bilayer interior. The channel lining exposes either charged (Asp, Glu, Arg, Lys) or polar-neutral (Ser, Thr) residues. A bundle of four parallel helices constrained to C4 symmetry, the helix axis aligned with the symmetry axis, and the helices constrained to idealized dihedral angles, produces a structure with a pore of the size inferred for the sodium channel protein (area ∼ 16 Å2). Similarly, a pentameric array optimized with constraints to maintain C5 symmetry and backbone torsions characteristic of α-helices adopts a structure that appears well suited to form the lining of the nicotinic cholinergic receptor (pore area ∼ 46 Å2). Thus, bundles of amphipathic α-helices satisfy the structural, energetic, and dynamic requirements to be the molecular structural motif underlying the function of ionic channels.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080305
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 139
    Electronic Resource
    Electronic Resource
    Masthead (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990) 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080401
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 140
    Electronic Resource
    Electronic Resource
    Refinement of the NMR structures for acyl carrier protein with scalar coupling data (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 377-385 
    Details
    ISSN: 0887-3585
    Keywords: structure deteremination ; two-dimensional NMR ; molecular mechanics ; molecular dynamics ; conformational equilibrium ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Structure determination of small proteins using NMR data is most commonly pursued by combining NOE derived distance constraints with inherent constraints based on chemical bonding. Ideally, one would make use of a variety of experimental observation, not just distance constraints. Here, coupling constant constraints have been added to molecular mechanics and molecular dynamics protocols for structure determination in the form of a psuedoenergy function that is minimized in a search for an optimum molecular conformation. Application is made to refinement of a structure for a 77 amino acid protein involved in fatty acid synthesis, Escherichia coli acyl carrier protein (ACP). 54 3JHNα coupling constants, 12 coupling constants for stereospecifically assigned side chain protons, and 450 NOE distance contraints were used to calculate the 3-D structure of ACP. A three-step protocol for a molecular dynamics calculation is described, in analogy to the protocol previously used in molecular mechanics calculations. The structures calculated with the molecular mechanics approach and the molecular dynamics apporach using a rigid model for the protein show similar molecular energies and similar agreement with experimental distance and coupling constant constraints. The molecular dynamics approach shows some advantage in overcoming local minimum problems, but only when a two-state averaging model for the protein was used, did molecular energies drop significantly.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080411
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 141
    Electronic Resource
    Electronic Resource
    Computer analysis of mutations that affect antibody specificity (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 93-98 
    Details
    ISSN: 0887-3585
    Keywords: protein conformation ; CONGEN ; immunoglobulin ; hydrogen bond ; digoxin ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The mouse hybridoma cell line 40-150 scretes antibodies with high affinity towards the cardiac glycosides digoxin and digitoxin. A spontaneous mutant, 40-150 A2.4, produces and antibody which carries a single residue mutation, Ser → Arg, in its heavy chain (H94) and has an altered specificity. A second order mutant 40-150 A2.4 P.10, produces two antibody molecules, one the same as 40-150 A2.4, the other lacking two residues at the N-terminus of its H chain, and having a specificity profile approaching that of 40-150 antibody. 1 The N-terminus and the position H94 are distant from the antigen-binding site of the antibody; thus, the structural basic of the specificity changes was not immediately clear. Approximate structures of the 40-150 antibody and its mutants were constructed in the computer, based on atomic coordinates of the homologous mouse antibody McPC 603. Using the program OCNGEN, the torsional space of the polypeptide backbone and side chains around position H94 was uniformly sampled, and the lowest energy conformations were analyzed in detail. The results indicate that when Arg-H94 is substituted for Ser. Agr-H94 can hydrogen bond to side chains of Asp-H101, Arg-L46, and Asp-L55. The results in a change in the surface of the combining site which may account for the affinity changes. Deletion of the two N-terminal residues increases solvent accessibility of Arg-H94. The solvation may cause a hydrogen bond between Arg-H94 and Asp-H101 to be lost, restoring the structure to one similar to that of 40-150.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070109
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 142
    Electronic Resource
    Electronic Resource
    Erratum (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 296-297 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070311
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 143
    Electronic Resource
    Electronic Resource
    Masthead (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990) 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070401
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 144
    Electronic Resource
    Electronic Resource
    Crystallographic refinement of human serum retinol binding protein at 2Å resolution (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 44-61 
    Details
    ISSN: 0887-3585
    Keywords: RBP ; RBP family ; protein structure ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Human serum retinol binding protein (RBP) in complex with retinol has been crystallographically refined to an R-factor of 18.1% with 2Å resolution data. The protein topology results in an anti-parallel β-barrel that encapsulates the retinol ligand. A detailed description of the protein and the binding site is provided. Our structural work has helped to define a family of proteins, many of which are carrier proteins for smaller ligand molecules. We describe the structural basis for the conservation of sequence within the family.
    Additional Material: 15 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080108
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 145
    Electronic Resource
    Electronic Resource
    The three-dimensional structure of recombinant bovine chymosin at 2.3 Å resolution (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 82-101 
    Details
    ISSN: 0887-3585
    Keywords: chymosin ; acid proteinase ; rennin ; X-ray structure ; structure comparison ; catalytic site ; crystal packing ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The crystal structure of recombinant bovine chymosin (EC 3.4.23.4; renin), which was cloned and expressed in Escherichia coli, has been determined using X-ray data extending to 2.3 Å resolution. The crystals of the enzyme used in this study belong to the space group I222 with unit cell dimensions a = 72.7 Å, b = 80.3 Å, and c = 114.8 Å. The structure was solved by the molecular replacement method and was refined by a restrained least-squares procedure. The crystallographic R factor is 0.165 and the deviation of bond distances from ideality is 0.020 Å. The resulting model includes all 323 amino acid residues, as well as 297 water molecules. The enzyme has an irregular shape with approximate maximum dimensions of 40 × 50 × 65 Å. The secondary structure consists primarily of parallel and antiparallel β-strands with a few short α-helices. The enzyme can be subdivided into N- and C- terminal domains which are separated by a deep cleft containing the active aspartate residues Asp-34 and Asp-216. The amino acid residues and waters at the active site form an extensive hydrogen-bonded network which maintains the pseudo 2-fold symmetry of the entire structure. A comparison of recombinant chymosin with other acid proteinases reveals the high degree of structural similarity with other members of this family of proteins as well as the subtle differences which make chymosin unique. In particular, Tyr-77 of the flap region of chymosin does not hydrogen bond to Trp-42 but protrudes out in the P1 pocket forming hydrophobic interactions with Phe-119 and Leu-32. This may have important implications concerning the mechanism of substrate binding and substrate specificity.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080110
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 146
    Electronic Resource
    Electronic Resource
    Conformational flexibility of a scorpion toxin active on mammals and insects: A circular dichroism study (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 164-172 
    Details
    ISSN: 0887-3585
    Keywords: protein secondary structure ; sodium channel ; CD spectra analysis program ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Three scorpion toxins have been analyzed by circular dichroism in water and in 2,2,2-trifluoroethanol (TFE) solutions. These toxins were chosen because they are representative of three kinds of pharmacological activities: (1) toxin AaH IT2, an antiinsect toxin purified from the venom of Androctonus australis Hector, which is able to bind to insect nervous system preparation, (2) toxin Css II, from the venom of Centruroides suffusus suffusus, which is a β-type antimammal toxin capable of binding to mammal nervous system preparation, and (3) the toxin Ts VII from the venom of Tityus serrulatus, which is able to bind to both types of nervous systems. In order to minimize bias, CD data were analyzed by a predictive algorithm to assess secondary structure content. Among the three molecules, Ts VII presented the most unordered secondary structure in water, but it gained in ordered forms when solubilized in TFE. These results indicated that the Ts VII backbone is the most flexible, which might result in a more pronounced tendency for this toxin molecule to undergo conformational changes. This is consistent with the fact that it competes with both antiinsect and β-type antimammal toxins for the binding to the sodium channel.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080206
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 147
    Electronic Resource
    Electronic Resource
    Functionally acceptable substitutions in two α-helical regions of λ repressor (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 306-316 
    Details
    ISSN: 0887-3585
    Keywords: neutral mutations ; random mutagenesis ; protein structure ; protein folding ; protein families ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A method of targeted random mutagenesis has been used in investigate the informational content of 25 residue positions in two α-helical regions of the N-terminal domain of λ repressor. Examination of the functionally allowed sequences indicates that there is a wide range in tolerance to amino acid substitution at these position. At position that are buried in the structure, there are severe limitations on the number and type of residues allowed. At most surface positions, many different residues and residue types are tolerated. However, at several surface positions there is a string preference for hydrophilic amino acids, and at one surface position proline is absolutely conserved. The results reveal the high level of degeneracy in the information that specifies a particular protein fold.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070403
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 148
    Electronic Resource
    Electronic Resource
    Crystal structure of subtilisin BPN′ variants containing disulfide bonds and cavities: Concerted structural rearrangements induced by mutagenesis (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 343-357 
    Details
    ISSN: 0887-3585
    Keywords: engineered disulfide groups ; X-ray structure ; hydrophobic cavities ; water structure, altered ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The X-ray structure of four genetically engineered disulfide variants of subtilisin have been analyzed to determine the energetic and structural constraints involved in inserting disulfide bonds into proteins. Each of the engineered disulfides exhibited atypical sets of dihedral angles compared with known structures of natural disulfide bridges in proteins and affected its local structural environment to a different extent. The disulfides located in buried regions, Cys26-Cys232 and Cys29-Cys87 and Cys22-Cys87, which are located on the surface of the molecule. An analysis of the concerted changes in secondary structure units such as α-helices and β-sheets indicated systematic long-range effects. The observed changes in the mutants were largely distributed asymmetrically around the inserted disulfides, reflecting different degrees of inherent flexibility of neighboring secondary structure types. The disulfide substitution in each variant molecule created some invaginations or cavities, causing a reorganization of the surrounding water structure. These changes are described, as well as the changes in side chain positions of groups that border the cavities.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070406
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 149
    Electronic Resource
    Electronic Resource
    Molecular interactions in protein crystals: Solvent accessible surface and stability (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 1-5 
    Details
    ISSN: 0887-3585
    Keywords: accessible area ; crystalline environment ; hydrophobic interaction ; linear correlation ; monomeric proteins ; dimeric proteins ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The accessible surface areas of 58 monomeric and dimeric proteins, when measured in the crystalline environment, are found to be simply related to molecular weight. The loss of accessible surface when the proteins go from a free to their crystalline environment is well defined, implying that the hydrophobic interaction, which has been found to contribute to protein folding and stability in living systems, also contributes to protein crystal stability.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080103
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 150
    Electronic Resource
    Electronic Resource
    Protein stability and electrostatic interactions between solvent exposed charged side chains (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 23-29 
    Details
    ISSN: 0887-3585
    Keywords: urea induced unfolding ; increased stability ; site-directed mutagenesis ; calbindin D9k ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: To investigate the contribution to protein stability of electrostatic interactions between charged surface residues, we have studied the effect of substituting three negatively charged solvent exposed residues with their side-chain amide analogs in bovine calbindin D9k - a small (Mr 8,500) globular protein of the calmodulin superfamily. The free energy of urea-induced unfolding for the wildtype and seven mutant proteins has been measured. The mutant proteins have increased stability towards unfolding relative to the wildtype. The experimental results correlate reasonably well with theoretically calculated relative free energies of unfolding and show that electrostatic interactions between charges on the surface of a protein can have significant effects on protein stability.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080106
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 151
    Electronic Resource
    Electronic Resource
    Amphipathic helix motif: Classes and properties (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 103-117 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080202
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 152
    Electronic Resource
    Electronic Resource
    Crystal structure of a protein-toxin α1-purothionin at 2.5Å and a comparison with predicted models (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 118-132 
    Details
    ISSN: 0887-3585
    Keywords: molecular modeling ; α1-purothionin ; x-ray structure determination ; molecular replacement ; comparison of crystal structure and predicted models ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: α1-Purothionin (α1-P), a wheatgerm protein and lytic toxin, has a secondary and tertiary structure similar to that of crambin as revealed by CD and NMR studies. α1-P crystallizes in the tetragonal space group I422 with unit cell dimensions: a = b = 53.59 and c = 69.79 Å. X-ray diffraction data have been measured to 2.5 Å Bragg spacing. The crystal structure has been determined by molecular replacement methods, using an energy-minimized α1-P model structure derived from crambin (Whitlow and Teeter: Journal of Biomolecular Structure and Dynamics 2:831-848, 1985, Journal of the American Chemical Society 108:7163-7172, 1986). The energy-minimized model gives a slightly cleaner rotation solution and better refinement against the x-ray data than do the crambin or unminimized α1-P structures. The final crystallographic residual with the data in the 10-2.5 Å resolution range is 0.216. The refined α1-P structure has a backbone rms difference of 0.74 Å from crambin and 0.55 Å from the energy-minimized α1-P model. A low resolution NMR model of α1-P calculated from metric matrix distance geometry and restrained molecular dynamics differs from crambin's backbone by 2.3 Å rms deviation (Clore et al.: EMBO Journal 5:2729-2735, 1986). Backbone dihedral angles for our predicted model differ from the refined α1-P structure in only one region (at a turn where there is a deletion relative to crambin). The NMR model had differences in four regions.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 153
    Electronic Resource
    Electronic Resource
    Three-Dimensionnal structures of complexes of Lathyrus ochrus isolectin I with glucose and mannose: Fine specificity of the monosaccharide-binding site (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 365-376 
    Details
    ISSN: 0887-3585
    Keywords: lectins ; crystal structure ; lectin specificity ; mannose ; glucose ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The structure of the methyl-α-D-mannopyranoside-LOL I complex has been solved by the molecular replacement method using the refined saccharide-free LOL I coordinates as starting model. The methyl-α-D-mannopyranoside-LOL I complex was refined by simulated annealing using the program X-PLOR. The final R-factor value is 0.182 [Fo 〉 1σ(Fo)]. The isostructural methyl-α-D-glucopyranoside-LOL I complex was refined by X-Ray coupled energy minimization using the methyl-α-D-mannopyranoside-LOL I structure as a starting model to an R factor of 0.179 (all data). In both crystal forms, each dimer binds two molecules of sugar in pockets found near the calcium ions. The two saccharide moieties, which are in the C1 chair conformation, establish the same hydrogen bond pattern with the lectin. However, the van der Walls contacts are different between the O2, C2, C6, and O6 atoms of the two molecules and the backbone atoms of residues 208-211. Mannose, due to its axial C2 conformation, encloses the backbone atoms of the protein in a clamplike way. Van der Waals energy calculations suggest that this better complementarity of the mannoside molecule with the lectin could explain its higher affinity for isolectin I.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080410
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 154
    Electronic Resource
    Electronic Resource
    Revised 2.3 Å structure of porcine pepsin: Evidence for a flexible subdomain (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 62-81 
    Details
    ISSN: 0887-3585
    Keywords: pepsin ; aspartic proteinases ; subdomains ; structure comparison ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A revised three-dimensional crystal structure of ethanol-inhibited porcine pepsin refined to an R-factor of 0.171 at 2.3 Å resolution is presented and compared to the refined structures of the fungal aspartic proteinases: penicillopepsin, rhizopuspepsin, and endothiapepsin. Pepsin is composed of two nearly equal N and C domains related by an intra dyad. The overall polypeptide fold and active site structures are homologous for pepsin and the fungal enzymes. The weak inhibition of pepsin by ethanol can be explained by the presence of one or more ethanol molecules, in the vicinity of the active site carboxylates, which slightly alter the hydrogen-bonding network and which may compete with substrate binding in the active site. Structural superposition analysis showed that the N domains aligned better than the C-domains for pepsin and the fungal aspartic proteinases: 107-140 Cα pairs aligned to 0.72-0.85 Å rms for the N domains; 64-95 Cα pairs aligned to 0.78-1.03 Å rms for the C domains. The major structural difference between pepsin and the fungal enzymes concerns a newly described subdomain whose conformation varies markedly among these enzyme structures. The subdomain in pepsin comprises nearly 100 residues and is composed of two contiguous segments within the C domain (residues 192-212 and 223-299). The subdomain is connected, or “hinged,” to a mixed β-sheet that forms one of the structurally invariant, active site ψ-loops. Relative subdomain displacements as large as a 21.0° rotation and a 5.9 Å translation were observed among the different enzymes. There is some suggestion in pepsin that the subdomain may be flexible and perhaps plays a structural role in mediating substrate binding, determining the substrate specificity, or in the activation of the zymogen.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080109
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 155
    Electronic Resource
    Electronic Resource
    Acid helix-turn activator motif (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 156-163 
    Details
    ISSN: 0887-3585
    Keywords: transcription activation ; secondary structure ; machine learning ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A common sequence/structural motif pattern has been identified within the steroid/thyroid hormone receptors and other transcriptional activators using a new massively parallel symbolic learning assistant computer system. The pattern appears nearly diagnostic of transcription activation, including relative activation strength, among nuclear and DNA-binding prokaryotic proteins. In cases where mutation/deletion/chimeric studies have identified the activation domain, the pattern matches within that domain. These facts and the nature of the pattern itself strongly support the idea that the patterned domain is directly involved in a protein-protein transcription activation interaction.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080205
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 156
    Electronic Resource
    Electronic Resource
    Preliminary crystallographic analysis of class 3 rat liver aldehyde dehydrogenase (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 305-308 
    Details
    ISSN: 0887-3585
    Keywords: aldehyde dehydrogenase ; crystals ; X-ray analysis ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: NAD-linked aldehyde dehydrogenases (A1DH) (EC 1.2.1.3) catalyze the irreversible oxidation of a wide variety of aldehydes to their respective carboxylic acids. Crystals of a class 3 A1DH (from an Escherichia coli expression system) suitable for X-ray analysis have been obtained. These crystals, which can be grown to a size of 0.8 × 0.3 × 0.2 mm, diffract to 2.5 Å resolution. Analysis of the diffraction pattern indicates that the crystals belong to the monoclinic space group P21, with cell parameters a = 65.11 Å, b = 170.67 Å, c = 47.15 Å, and β = 110.5°. Assuming one dimer per asymmetric unit, the value Vm is calculated to be 2.45 and the solvent content of the crystal is estimated to be 50%. A self-rotation function study produced significant rotation peaks (58% of the origin) on the K = 180 section at ψ = 90° and φ = 71° and 341°, indicating that the pseudo-dimer axis is (or is very nearly) perpendicular to the b-axis.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080404
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 157
    Electronic Resource
    Electronic Resource
    Plastic adaptation toward mutations in proteins: Structural comparison of thymidylate synthases (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 315-333 
    Details
    ISSN: 0887-3585
    Keywords: thymidylate synthase ; plasticity ; crystal structure ; B factor ; mutation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The structure of thymidylate synthase (TS) from Escherichia coli was solved from cubic crystals with a = 133 Å grown under reducing conditions at pH 7.0, and refined to R = 22% at 2.1 Å resolution. The structure is compared with that from Lactobacillus casei solved to R = 21% at 2.3 Å resolution. The structures are compared using a difference distance matrix, which identifies a common core of residues that retains the same relationship to one another in both species. After subtraction of the effects of a 50 amino acid insert present in Lactobacillus casei, differences in position of atoms correlate with temperature factors and with distance from the nearest substituted residue. The dependence of structural difference on thermal factor is parameterized and reflects both errors in coordinates that correlate with thermal factor, and the increased width of the energy well in which atoms of high thermal factor lie. The dependence of structural difference on distance from the nearest substitution also depends on thermal factors and shows an exponential dependence with half maximal effect at 3.0 Å from the substitution. This represents the plastic accommodation of the protein which is parameterized in terms of thermal B factor and distance from a mutational change.
    Additional Material: 16 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080406
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 158
    Electronic Resource
    Electronic Resource
    Announcement (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 404-405 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080414
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 159
    Electronic Resource
    Electronic Resource
    Masthead (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990) 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080301
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 160
    Electronic Resource
    Electronic Resource
    Conformational and helicoidal analysis of the molecular dynamics of proteins: “Curves,” dials and windows for a 50 psec dynamic trajectory of BPTIEditors note: The authors submitted an entire data set, and agreed to publish in this article only the first panel in each of Figures 9 through 12. The entire data set in these figures is available from David Beveridge or Richard Lavery upon request. (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 179-193 
    Details
    ISSN: 0887-3585
    Keywords: protein conformation ; helicoidal parameters ; molecular dynamics ; bovine pancreatic trypsin inhibitor ; simulation ; protein-protein interactions ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A new procedure for the graphic analysis of molecular dynamics (MD) simulations on proteins is introduced, in which comprehensive visualization of results and pattern recognition is greatly facilitated. The method involves determining the conformational and helicoidal parameters for each structure entering the analysis via the method “Curves,” developed for proteins by Sklenar, Etchebest, and Lavery (Proteins: Structure, Function Genet. 6:46-60, 1989) followed by a novel computer graphic display of the results. The graphic display is organized systematically using conformation wheels (“dials”) for each torsional parameter and “windows” on the range values assumed by the linear and angular helicoidal parameters, and is present in a form isomorphous with the primary structure per se. The complete time evolution of dynamic structure can then be depicted in a set of four composite figures. Dynamic aspects of secondary and tertiary structure are also provided. The procedure is illustrated with an analysis of a 50 psec in vacuo simulation on the 58 residue protein, bovine pancreatic trypsin inhibitor (BPTI), in the vicinity of the local minimum on the energy surface corresponding to a high resolution crystal structure. The time evolution of 272 conformational and 788 helicoidal parameters for BPTI is analyzed. A number of interesting features can be discerned in the analysis, including the dynamic range of conformational and helicoidal motions, the dynamic extent of 2° structure motifs, and the calculated fluctuations in the helix axis. This approach is expected to be useful for a critical analysis of the effects of various assumptions about force field parameters, truncation of potentials, solvation, and electrostatic effects, and can thus contribute to the development of more reliable simulation protocols for proteins. Extensions of the analysis to present differential changes in conformational and helicoidal parameters is expected to be valuable in MD studies of protein complexes with substrates, inhibitors, and effectors and in determining the nature of structural changes in protein-protein interactions.
    Additional Material: 15 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080208
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 161
    Electronic Resource
    Electronic Resource
    Normal mode analysis of human lysozyme: Study of the relative motion of the two domains and characterization of the harmonic motion (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 258-279 
    Details
    ISSN: 0887-3585
    Keywords: topology of atom packing ; hinge bending motion ; accessible surface area ; elastic deformation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A normal mode analysis of human lysozyme has been carried out at room temperature. Human lysozyme is an enzyme constituted of two domains separated by an active site cleft, the motion of which is thought to be relevant for biological function. This motion has been described as a hinge bending motion. McCammon et al.1 have determined the characteristics of the hinge bending motion but they assumed a prior knowledge of the hinge axis. In this work we propose a method which is free from this assumption and determines the hinge axis and root mean square (rms) rotation angle which give the best agreement with the pattern of changes in all the distances between nonhydrogen atoms in the two domains, obtained by the normal mode analysis. The hinge axis we found is notably different from the one previously determined and goes, roughly, through the Cα 55 and Cα 76, i.e., it is located at the base of the β-sheet of the second domain. The rms value for the rotation angle is also twice as large as the previous one: 3.37°. It is shown that this hinge bending motion provides a fairly good approximation of the dynamics of human lysozyme and that the normal mode with the lowest frequency has a dominating contribution to this hinge bending motion.A study of the accessible surface area of the residues within the cleft reveals that the motion does not result in a better exposure to the solvent of these residues.A characterization of the thermally excited state (under the hypothesis of the harmonicity of the potential energy surface) has been done using the concept of topology of atom packing. Under this hypothesis the thermal fluctuations result only in a small change of the topology of atom packing, leading therefore to nearly elastic deformations of the protein.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080308
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 162
    Electronic Resource
    Electronic Resource
    The effect of solvent viscosity on the rate-determining step of fatty acid synthetase (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 287-293 
    Details
    ISSN: 0887-3585
    Keywords: fatty acid synthetase ; overall activity ; viscogens ; diffusion limited intramolecular motion ; rate-determining step ; microviscosity ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The overall activity of animal fatty acid synthetase at the saturation level of substrate concentration decreased when the solvent viscosity, η, of the reaction mixture was increased with viscogens such as glycerol, sucrose, and polyethylene glycol. The activity of the enzyme changed roughly proportional to η-p, where p = 1.0 for glycerol, p = 0.66 for sucrose, and p 〈 0.6 for polyethylene glycol with different molecular sizes. The thioesterase activity, which catalyzes the final partial reaction in the multifunctional enzyme, was not affected by 5-fold increase of solvent viscosity with sucrose. These results suggested that the rate-determining step of the enzyme other than the thioesterase reaction involves a microscopic transport step, the rate of which is influenced by the solvent viscosity. The microscopic transport step may be related to the transfer of the reaction intermediate from one active site to another or to the motion of a larger part of the enzyme requisite for the catalytic reaction. In the solution containing glycerol, the rate-determining motion was primarily diffusion limited since the inverse of the initial rate was proportional to η, i.e., p = 1. Since the substrate concentration was at a saturation level in this experiment, the viscosity-dependent step cannot be the encounter between the enzyme and substrates, but must be intramolecular in origin, most probably the reaction catalyzed by β-ketoacyl synthetase. In solutions containing other viscogens, however, p was less than 1.0, indicating a significant involvement of chemical steps in the rate-determining step as well. Bovine serum albumin, when used as a proteinic viscogen, also decreased the initial rate. In the living cells therefore, the rate-determining intramolecular motion of fatty acid synthetase could be affected by the presence of high concentrations of cytoplasmic proteins.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080310
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 163
    Electronic Resource
    Electronic Resource
    Functional interaction among catalytic residues in subtilisin BPN′ (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 335-342 
    Details
    ISSN: 0887-3585
    Keywords: serine protease ; catalytic triad ; oxyanion binding site ; site-directed mutagenesis ; protease inhibitor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Variant of the serine protease, subtilisin BPN′, in which the catalytic triad residues (Ser-221, His-64, and Asp-32) are replaced singly or in combination by alanine retain activities with the substrate N-succinyl-L-Ala-L-Ala-L-Pro-L-Phe-p-nitroanilide (sAAPF-pna) that are at at least 103 to 104 above the non-enzymatic rate [Carter, P., Wells, J.A. Nature (London) 322:564-568, 1988]. A possible source of the residual activity was the hydrogen bond with the Nδ2 of Asn-155 that helps to stabilize the oxyanion generated in the tetrahedral transition state during amide bond hydrolysis by the wild-type enzyme. Replacing Asn-155 by Gly (N155G) lowers the turnover number (kcat) for sAAPF-pna by 150-fold with virtually no change in the Michaelis constant (KM). However, upon combining the N155G and S221A mutations to give N155G:S221A, kcat is actually 5-fold greater than for the S221A enzyme. Thus, the catalytic role of Asn-155 is dependent upon the presence of Ser-221. The residual activity of the N155G:S221A enzyme (∼104-fold above the uncatalyzed rate) is not an artifact because it can be completely inhibited by the third domain of the turkey ovomucoid inhibitor (OMTKY3), which forms a strong 1:1 complex with the active site. the mutations N155G and S221A individually weaken the interaction between subtilisin and OMTKY3 by 1.8 and 2.0 kcal/mol, respectively, and in combination by 2.1 kcal/mol. This is consistent with disruption of stabilizing interactions around the reactive site carbonyl of the OMTKY3 inhibitor. These data suggest that Ser-221 functions together with Asn-155 to accelerate amide bond hydrolysis and that other transition state stabilizing interactions account for the residual rate enhancement of 103- to 104-fold. More generally, these studies illustrate the limitations of using site-directed mutagenesis to probe the energetic importance of a single catalytic group whose function is dependent upon the interaction with others.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070405
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 164
    Electronic Resource
    Electronic Resource
    Masthead (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990) 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080101
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 165
    Electronic Resource
    Electronic Resource
    Hydrophobicity of amino acid subgroups in proteins (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 6-13 
    Details
    ISSN: 0887-3585
    Keywords: hydrophobicity ; hydrophobic effect ; protein folding ; solvent accessibility ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Protein folding studies often utilize areas and volumes to assess the hydrophobic contribution to conformational free energy (Richards, F. M. Annu. Rev. Biophys. Bioeng. 6:151-176, 1977). We have calculated the mean area buried upon folding for every chemical group in each residue within a set of X-ray elucidated proteins. These measurements, together with a standard state cavity size for each group, are documented in a table. It is observed that, on average, each type of group buries a constant fraction of its standard state area. The mean area buried by most, though not all, groups can be closely approximated by summing contributions from three characteristic parameters corresponding to three atom types: (1) carbon or sulfur, which turn out to be 86% buried, on average; (2) neutral oxygen or nitrogen, which are 40% buried, on average; and (3) charged oxygen or nitrogen, which are 32% buried, on average.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080104
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 166
    Electronic Resource
    Electronic Resource
    Role of phosphorylation in conformational adaptability of bovine myelin basic protein (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 32-40 
    Details
    ISSN: 0887-3585
    Keywords: myelin basic protein ; phosphorylation ; protein conformation ; β-structure ; thrombin ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Controlled thrombic digestion of a preparation of components 2 + 3 isolated from the 18.5 kDa bovine myelin basic protein (MBP) yielded a polypeptide that was monophosphorylated on threonine 97 (component 3pT97). This is the first posttranslationally phosphorylated MBP isolated in pure form. We studied the effect of this single phosphate on the conformational adaptability of 18.5 kDa bovine MBP by comparing the circular dichroism (CD) spectrum of component 3pT97 with the spectra of highly purified nonphosphorylated components 1 and 2. The CD spectra of nonphosphorylated component 1 and component 2 [monodeamidated forms(s) of component1] were indistinguishable, while component 3pt97 exhibited a different spectrum. The singly phophorylated MBP component exhibited 13% more ordered conformations than that adopted by nonphosphorylated MBP in dilute aqueous solutions. This was estimated from the CD spectra, and apparently involved about 17 additional amino acid residues in β-structure(s).
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070104
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 167
    Electronic Resource
    Electronic Resource
    Apolar peptide models for conformational heterogeneity, hydration, and packing of polypeptide helices: Crystal structure of hepta- and octapeptides containing α-aminoisobutyric acid (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 62-73 
    Details
    ISSN: 0887-3585
    Keywords: hydrophobic α-helices ; water insertion into helix ; water in hydrophobic pocket ; helix unfolding ; helix folding ; parallel packing ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The crystal structures of two helical peptides Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe (VALU-7) and Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe (VALU-8) have been determined to a resolution of 1.0 and 0.9 Å, respectively. Both the seven and eight residue peptides crystallize with two conformers per asymmetric unit. The VALU-8 conformers are completely helical and differ only at the C-terminus by a sign reversal of the φ, ψ angles of the last residue. One of the VALUE-7 conformers occurs as a normal α-helix, whereas in the other, the N(7)=O(3) α-type hydrogen bond is ruptured by the entry of a water molecule (W) into the helix, which in turn makes hydrogen bonds N(7)⃛W = 2.97 Å and ⃛O(3) = 2.77 Å. The other side of the water molecule is surrounded by a hydrophobic pocket. These two conformers give a static representation of a step in a possible helix unwinding or folding process. In the value-8 crystal the helices aggregate in a parallel mode, whereas the aggregation is antiparallel in the VALU-7 crystal. The crystal parameters are VALUE-7 crystal. The crystal parameters are VALUE-7, P21, a = 10.203 (3) Å, b = 19.744 (6) Å, c = 22.561 (6) Å, α = 96.76°, Z = 4, C38, H69N7O10·0.5 H2O, R = 6.65% for 3674 reflections observed 〉3σ(F): and VALU-8, P21, a; = 10.596 (4) Å, b = 27.57 (6) Å, c = 17.745 (5) Å, β = 95.76 (3)°, Z = 4, C42H76N76O11·0.25 CH3OH, R = 6.63% for 4701 reflections observed 〉3σ(F).
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070107
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 168
    Electronic Resource
    Electronic Resource
    On the nature of antibody combining sites: Unusual structural features that may confer on these sites an enhanced capacity for binding ligands (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 112-124 
    Details
    ISSN: 0887-3585
    Keywords: amino acid propensities ; aromatic residues ; conformational entropy ; exposure patterns ; interaction energy ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A detailed analysis of the structural aspects of antibody-antigen interactions has been made possible by the availability of X-ray structures for three complexes of antilysozyme Fabs to lysozyme (reviewed by Davies et al: J. Biol. Chem. 263:10541-10544, 1988.) Examination of the antigen-contacting residues in the three antilysozyme Fabs reveals the occurrence of a large number of aromatics, particularly tyrosines, and the absence of apolar, aliphatic residues. Calculation of the frequency of occurrence of the various amino acids types reveals that tyrosines are three times, and histidines and asparagines eight times, more likely to be found in the complementarity-determinig regions that in the framework of the variability of the residue in FVs (the modules containing variable domains of the light and heavy chains) of known three-dimensional structure indicates that tryosines and tryptophans are more exposed when they occur in the complementarity-determining regions that when in the framework. Furthermore, many more of the asparagines in the complementarity-determining regions than in the framework are buried. These aspararagines appear to have a structural role in that they hydrogen bond through their side chains to other side chains and, Even more so, to the protein backbone. The stabilizing effect of the asparragines, plus the rigidity of the framework, may serve to allow the greater exposure of the aromatic residues to solvent. In view of the greater potential contribution of aromatic side chains to the total binding energy, these results suggest that antibody-combining sites have structural features that make them especially studied for interacting with lagands.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 169
    Electronic Resource
    Electronic Resource
    Masthead (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990) 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070301
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 170
    Electronic Resource
    Electronic Resource
    Solution structure of a zinc finger domain of yeast ADR1 (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 7 (1990), S. 215-226 
    Details
    ISSN: 0887-3585
    Keywords: zinc finger ; DNA-binding motif ; two-dimensional NMR ; synthetic peptides ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The “zinc finger” is a 30-residue repeating motif that has been identified in a variety of eukaryotic transcription factors. Each domain is capable of binding a Zn2+ ion through invariant Cys and His residues. We have determined the three-dimensional structure of a synthetic peptide that corresponds to one of the two zinc finger domains in the yeast transcription factor ADR1, using two-dimensional nuclear magnetic resonance spectroscopy. The Zn2+ -bound structure of the peptide consists of a loop containing the two Cys residues, a “fingertip,” a 12- to 13-residue α-helix containing the two His residues, and a C-terminal tail. A majority of the interrresidue contacts observed invlove the seven conserved residues of the prototypic zinc finger (i.e., four zinc ligands and the three hydrophobic residues), indicating that these residues are largely responsible for the three-dimensional structure of the domain and that all the zinc finger domains of the TFIIIA class will have similar structures, with the highest concentration of such residues on the external face of the α-helix.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340070303
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 171
    Electronic Resource
    Electronic Resource
    Generation of potential structures for the G-domain of chloroplast EF-Tu using comparative molecular modeling (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 237-250 
    Details
    ISSN: 0887-3585
    Keywords: elongation factor ; energy minimization ; G-protein ; Guanine nucleotide binding ; protein structure ; protein synthesis ; structural homology ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Comparative molecular modeling has been used to generate several possible structures for the G-domain of chloroplast elongation factor Tu (EF-Tuchl) based on the crystallographic data of the homologous E. coli protein. EF-Tuchl contains a 10 amino acid insertion not present in the E. coli protein and this region has been modeled based on its predicted secondary structure. The insertion appears to lie on the surface of the protein. Its orientation could not be determined unequivocally but several likely structures for the nucleotide binding domain of EF-Tuchl have been developed. The effects of the presence of water in the Mg2+ coordination sphere and of the protonation sate of the GDP ligand on the conformation of the guanine nucleotide binding site have been examined. Relative binding constants of several guanine nucleotide analogs for EF-Tuchl have been obtained. The interactions between EF-Tuchl and GDP predicted to be important by the models that have been developed are discussed in relation to the nucleotide binding properties of this factor and to the interactions proposed to be important in the binding of guanine nucleotides to related proteins.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080306
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 172
    Electronic Resource
    Electronic Resource
    In memoriam (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. i 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080402
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 173
    Electronic Resource
    Electronic Resource
    Hormone phage: An enrichment method for variant proteins with altered binding properties (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 309-314 
    Details
    ISSN: 0887-3585
    Keywords: hormone-receptor interactions ; epitope libraries ; binding selection ; fusion phage ; human growth hormone ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Human growth hormone (hGH), a 191 residue protein containing two disulfide bonds, was fused to the carboxyl-terminal domain of the gene III protein, a minor coat protein exposed at one end of the filamentous phage M13. The gene fusion was cloned into a plasmid containing origins of replication for Escherichia coli and filamentous phage and was packaged into phagemid particles upon infection by an M13KO7 helper phage. Transcription of the hGH-gene III fusion was controlled so that usually no more than one copy of the fusion protein was displayed along with the four copies of the wild-type gene III protein. The hGH-gene III fusion protein was properly folded, as judged by reactivity with six hGH monoclonal antibodies whose epitopes are sensitive to the folded conformation of hGH. Moreover, the hGH-gene III phagemid particles were enriched over 5000-fold from non-hGH phage, and 8-fold from a mutant hGH phagemid following a single hGH-specific elution step from hGH receptor-coated beads. The hGH phagemid should be useful for isolating new receptor binding mutants of hGH. More generally, this expression system may allow other large proteins with discontinuous binding epitopes to be displayed, and binding selections applied to their mutated gene III fusions on filamentous phage.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080405
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 174
    Electronic Resource
    Electronic Resource
    Erratum (1990)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 8 (1990), S. 398-399 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340080413
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 175
    Electronic Resource
    Electronic Resource
    A phase I and pharmacokinetic study of intravenous vinzolidine (1990)
    Springer
    Investigational new drugs 8 (1990), S. S51 
    Details
    ISSN: 1573-0646
    Keywords: vinzolidine ; phase I ; pharmacokinetics ; melanoma ; renal cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The semi-synthetic vinca alkaloid vinzolidine was administered to advanced cancer patients as an intravenous bolus on a three day schedule every 21 days. Forty-two patients were treated in this phase I trial. Five partial remissions (breast-1, melanoma-2, renal cancer-2) were seen in 30 evaluable patients. The dose limiting toxicities were myelosuppression and neuropathy. Erratic myelosuppression from course to course within the same patient as seen in previous trials with oral vinzolidine, was not observed with the intravenous formulation. The measured pharmacokinetic parameters conformed best to a 2-compartment model with a mean terminal half-life of 23 hours. The anti-tumor activity observed during this phase I trial and acceptable toxicity provide the basis for initiating phase II studies in selected forms of cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00171984
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 176
    Electronic Resource
    Electronic Resource
    The Pharmacokinetics of β-Cyclodextrin and Hydroxypropyl-β-cyclodextrin in the Rat (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 1248-1252 
    Details
    ISSN: 1573-904X
    Keywords: β-cyclodextrin ; hydroxypropyl-β-cyclodextrin ; pharmacokinetics ; absorption ; intravenous administration ; oral administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Hydroxypropyl-β-cyclodextrin was analyzed by HPLC using postcolumn complexation with phenolphthalein and negative colorimetric detection, with a detection limit of 20 µg/ml. The pharmacokinetics of β-cyclodextrin and of hydroxypropyl-β-cyclodextrin were studied after intravenous administration to permanently cannulated rats. The pharmacokinetic behavior of both cyclodextrins was similar to that of inulin, showing rapid distribution over extracellular fluids. Elimination occurred through glomerular filtration. When a dose of 200 mg/kg β-cyclodextrin was administered the elimination rate was decreased, probably as a result of nephrotoxicity of β-cyclodextrin. Within 24 hr after administration most of the cyclodextrin dose was recovered unchanged in urine. After oral administration, only insignificant amounts of intact β-cyclodextrin were absorbed from the gastrointestinal tract.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015929720063
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 177
    Electronic Resource
    Electronic Resource
    Formulation and in Vitro-in Vivo Evaluation of Sustained-Release Lithium Carbonate Tablets (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 359-363 
    Details
    ISSN: 1573-904X
    Keywords: lithium ; sustained release ; pharmacokinetics ; bioavailability ; in vitro
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The release of lithium carbonate incorporated into polymethylmethacrylate, poly vinyl chloride, hy-drogenated vegetable oil, and carbomer matrix tablets was studied in vitro. The formulation containing 10% carbomer showed a sustained-release profile comparable to that of a standard, commercially available, sustained-release preparation containing 400 mg lithium carbonate embedded in a composite material. In vivo the newly formulated and standard sustained-release lithium carbonate tablets were compared to an oral solution and conventional lithium carbonate tablets in 12 healthy subjects. These crossover studies showed that the sustained-release tablets produced a flatter serum concentration curve than the oral solution and conventional tablet, without loss of total bioavailability.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015863204732
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 178
    Electronic Resource
    Electronic Resource
    Evaluation of Free Tissue Concentrations of Fleroxacin After Oral Administration (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 422-424 
    Details
    ISSN: 1573-904X
    Keywords: fleroxacin ; pharmacokinetics ; tissue concentrations ; blister fluid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015840027022
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 179
    Electronic Resource
    Electronic Resource
    Probenecid Inhibits the Metabolic and Renal Clearances of Zidovudine (AZT) in Human Volunteers (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 411-417 
    Details
    ISSN: 1573-904X
    Keywords: zidovudine ; pharmacokinetics ; probenecid ; AIDS therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effect of probenecid on the disposition of AZT was investigated in a pilot study in two healthy volunteers. The pharmacokinetics of AZT were examined after a single oral dose of 200 mg with and without probenecid coadministration in a balanced crossover study. Administration of 500 mg probenecid every 6 hr prior to and during AZT dosing resulted in an increase in the average AUCAZT from 89 µg · min/ml (control) to 191 µg · min/ml during probenecid treatment. This was manifested by a corresponding decrease in CLTOT/F, which is attributed to the inhibitory effect of probenecid on the glucuronidation and renal excretion of AZT. Average CLR and CLTOT/F of AZT decreased from 4.76 and 28.7 to 2.98 and 14.1 ml/min/kg during control and probenecid treatment, respectively. AZT glucuronidation was affected to a greater extent than its renal excretion, as reflected by the decreased ratio of GAZT/AZT urinary recoveries. The terminal half-life of AZT was slightly longer during probenecid administration. That only a small change in the half-life occurred indicates that probenecid also reduced the volume of distribution of AZT. The CLR of GAZT decreased from an average of 11.3 ml/min/kg (control) to 2.63 ml/min/kg during probenecid treatment, resulting in a greater than 3.5-fold increase in AUCGAZT. Probenecid did not affect the blood/plasma distribution or the plasma protein binding of AZT. These preliminary findings suggest that it may be possible to maintain effective plasma AZT concentrations in AIDS patients receiving a reduced daily dose, in combination with probenecid.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015835826114
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 180
    Electronic Resource
    Electronic Resource
    Constant-Rate Intravenous Infusion Methods for Estimating Steady-State Volumes of Distribution and Mean Residence Times in the Body for Drugs Undergoing Reversible Metabolism (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 628-632 
    Details
    ISSN: 1573-904X
    Keywords: intravenous infusion ; volume of distribution ; mean residence time ; reversible metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Equations for the steady-state volumes of distribution (V ss) and the mean residence times in the body (MRT) are derived for a drug and its metabolite subject to reversible metabolism and separately infused intravenously at a constant rate to steady state of both compounds. The V ss and MRT parameters are functions of the integrals of plasma concentrations, plasma concentrations at steady state, and times to reach steady state of both drug and metabolite. In addition, the MRT values are functions of the infusion rates. These equations were validated by computer simulations and comparison with IV bolus dose parameters. These relationships extend the ability to assess the pharmacokinetics of linear reversible metabolic systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015874329265
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 181
    Electronic Resource
    Electronic Resource
    Influence of Absorption Rate, Dosing Frequency, and Intrinsic Pharmacokinetic Profile on Steady-State Drug Concentrations (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 677-680 
    Details
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; absorption rate ; diurnal variation ; dosing frequency ; steady-state concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015894901040
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 182
    Electronic Resource
    Electronic Resource
    A Sensitive and Specific Liquid-Chromatographic Assay for Determination of Ganciclovir in Plasma and Urine and Its Application to Pharmacokinetic Studies in the Rabbit (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 1113-1118 
    Details
    ISSN: 1573-904X
    Keywords: ganciclovir ; analysis ; pharmacokinetics ; rabbit model ; renal secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A liquid-chromatographic assay for the analysis of ganciclovir in plasma and urine is described. This assay involves the use of acyclovir, an antiviral drug structurally related to ganciclovir, as the internal standard. A two-step sample preparation method is used. After protein is precipitated with acetonitrile and the addition of diethyl ether, ganciclovir and the internal standard are back extracted into a small volume of aqueous ammonium phosphate, taking advantage of their relatively high water solubility. This isocratic method is specific and sufficiently sensitive to allow quantification of ganciclovir throughout the entire range of concentrations observed during therapeutic use of this antiviral drug. There was no interference from various over-the-counter and prescription drugs often prescribed to patients most likely to receive ganciclovir therapy. This assay was used to analyze plasma and urine samples obtained after intravenous administration of ganciclovir to rabbits. Biexponential decay of ganciclovir plasma concentration–time and urinary excretion rate–time profiles was observed, with a mean distribution half-life of 15.8 min and an elimination half-life of 96 min. The mean renal clearance, 9.0 ml/min per kg, exceeds the glomerular filtration rate in the rabbit, indicating that ganciclovir is actively secreted in the renal tubule. Similar results were obtained by determining the renal clearance at steady state during constant-rate intravenous infusion of ganciclovir.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015920023272
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 183
    Electronic Resource
    Electronic Resource
    Evaluation of the Pharmacokinetic Interaction Between Diazepam and ACC-9653 (a Phenytoin Prodrug) in Healthy Male Volunteers (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 1172-1176 
    Details
    ISSN: 1573-904X
    Keywords: diazepam ; phenytoin ; ACC-9653 ; prodrug ; protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The protein binding and pharmacokinetics of diazepam, ACC-9653 (a phenytoin prodrug), and phenytoin were evaluated in nine healthy male volunteers following administration of diazepam and ACC-9653, alone or concomitantly, in a randomized crossover design. No significant differences were observed in the fraction unbound or pharmacokinetic parameters of ACC-9653, phenytoin, or diazepam when ACC-9653 was administered alone compared to concomitant administration with diazepam. The phenytoin fraction unbound increased significantly with increased concentrations of ACC-9653, indicating displacement of phenytoin from its binding sites by ACC-9653. ACC-9653 also demonstrated concentration dependent binding. The lack of a significant pharmacokinetic drug interaction between ACC-9653 and diazepam suggests that these drugs may be safely administered together, although this conclusion should be confirmed in the intended patient population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015940527815
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 184
    Electronic Resource
    Electronic Resource
    An Experimental Model for Measuring Middle Ear Antimicrobial Drug Penetration in Otitis Media (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 1242-1247 
    Details
    ISSN: 1573-904X
    Keywords: otitis media ; pharmacokinetics ; amoxicillin ; trimethoprim ; sulfamethoxazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Bacteria are an important cause of acute otitis media and successful treatment depends on achieving inhibitory or bacteriacidal antimicrobial drug concentrations in the middle ear. To evaluate further otitis media treatment success and failure, we developed a chinchilla model to study antimicrobial drug penetration through the middle ear mucosa. Using quantitative histomorphometry, we measured the middle ear space in 10 chinchillas and found a mean ±SD volume of 2.09 ± 0.08 ml and a mean SD surface area of 14.41 ± 1.48 cm2. To measure the apparent rate constant (K e) of antibiotic elimination from the middle ear, through the middle ear mucosa, an antibiotic solution was inoculated into the middle ear cavity, and samples were aspirated between 1 and 8 hr later. In normal ears, the mean K e ±SD for amoxicillin was 0.118 ± 0.013 hr−1, that for a trimethoprim 0.461 ± 0.090 hr−1, and that for sulfamethoxazole 0.265 ± 0.062 hr−1. In ears inoculated with type 7F Streptococcus pneumoniae to induce acute otitis media, the K e ±SD increased for all three drugs (P 〈 0.05): amoxicillin to 0.286 ± 0.089 hr−1, trimethoprim to 0.662 ± 0.118 hr−1, and sulfamethoxazole to 0.411 ± 0.056 hr−1. These values demonstrate that amoxicillin had the lowest apparent penetration rate constant of the three antibiotics but the greatest increase from normal to infected mucosa (142%). Trimethoprim had the highest apparent penetration rate constant of the three antibiotics but the smallest increase from normal to infected mucosa (44%), while the sulfamethoxazone apparent penetration rate constant increased from normal to infected mucosa by 55%. The K e for amoxicillin was the same for inoculation volumes of 0.8 and 1.6 ml (P = 0.557) and the same for sampling intervals of 4 and 8 hr (P = 0.054). All three antimicrobial drug concentration–time curves were log-linear, as predicted by Fick's first law of diffusion. In conclusion, this model overcomes the technical limitations of previous models and permits investigation of the many factors that can influence antibiotic penetration into the middle ear and reduce otitis media treatment efficacy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015977603224
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 185
    Electronic Resource
    Electronic Resource
    Hydralazine Pharmacokinetics and Interaction with Food: An Evaluation of the Dog as an Animal Model (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 274-279 
    Details
    ISSN: 1573-904X
    Keywords: hydralazine ; food–drug interaction ; Michaelis–Menten kinetics ; bioavailability ; pharmacokinetics ; dog ; animal model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The intravenous and oral dose-dependent pharmacokinetics of hydralazine and the effect of concurrent administration of food with hydralazine in dogs were evaluated for comparison with published human data. Four dogs were given intravenous and oral doses of hydralazine at 0.25, 1.0, 2.5, and 4.0 mg/kg. In addition, the oral 2.5 mg/kg dose was given with a meal. Blood samples were collected at appropriate intervals and analyzed for hydralazine. Pharmacokinetic analysis showed that AUCoral/ dose (5552 to 13218 mg-min/ml) and F (0.36 to 0.77) increased significantly with dose, indicating saturation of first-pass metabolism, as is seen in humans. Total-body clearance (70 ml/min/kg) and steady-state volume of distribution (9 L/kg) were similar to human values. The bioavailability of hydralazine in the dog was decreased by 63% when the dose was given with a meal, which is comparable to some human data. It was concluded that the dog may be a useful model in which to study mechanisms of the hydralazine-food interaction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015830330231
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 186
    Electronic Resource
    Electronic Resource
    Dose-Dependent Pharmacokinetics of Carbamazepine in Rats: Determination of the Formation Clearance of Carbamazepine-10,11-epoxide (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 513-517 
    Details
    ISSN: 1573-904X
    Keywords: carbamazepine ; carbamazepine-10,11-epoxide ; pharmacokinetics ; dose dependency ; metabolite ; blood
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The dose dependency of carbamazepine pharmacokinetics was characterized in rats, a common test animal for antiepileptic drug efficacy. With a randomized Latin square schedule, 5, 10, and 20 mg/kg doses of carbamazepine were injected intravenously into six Sprague-Dawley rats followed by the administration of a 5 or 10 mg/kg i.v. dose of CBZ-E to each rat. Following administration, the concentrations of CBZ and Carbamazepine-10,11-epoxide (CBZ-E) in whole blood were determined by a reverse-phase HPLC assay. Plasma protein binding of both carbamazepine and CBZ-E was linear over the concentration range observed in this study. Carbamazepine concentration–time plots were log-linear, but the slopes were not parallel. Carbamazepine total-body clearances were 15.1 ± 3.26, 13.4 ± 5.66, and 10.0 ± 3.11 ml/min/kg at the 5, 10, and 20 mg/kg doses, respectively (significance of difference between the 5 and the 20 mg/kg dose = 0.06 〈 P 〈 0.05; Kruskal–Wallis test, Dunn's procedure). However, the formation clearance to CBZ-E did not change, suggesting that metabolism via other pathways was decreased at higher carbamazepine doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015872901523
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 187
    Electronic Resource
    Electronic Resource
    Influence of Food on the Bioavailability of Ro 15-0778 in Humans (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 777-779 
    Details
    ISSN: 1573-904X
    Keywords: arotinoid ; bioavailability ; food effect ; pharmacokinetics ; humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015836110126
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 188
    Electronic Resource
    Electronic Resource
    Differential Effects of Anesthetic Regimens on Gentamicin Pharmacokinetics in the Rat: A Comparison with Chronically Catheterized Conscious Animals (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 41-45 
    Details
    ISSN: 1573-904X
    Keywords: gentamicin ; carboxyinulin ; pharmacokinetics ; anesthesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The intravenous disposition of gentamicin was compared in the conscious chronically catheterized rat with that in rats anesthetized using five injectable laboratory anesthetics. Gentamicin plasma clearance in the conscious rat was significantly higher than in animals anesthetized with urethane, fentanyl/ fluanisone/midazolam, pentobarbitone, or ketamine/midazolam but similar to that in rats anesthetized with alphaxolone/alphadolone. Urethane anaesthesia resulted in a significantly lower gentamicin clearance than in all other groups. Gentamicin clearance in rats anesthetized with alphaxolone/alphadolone was significantly higher than in rats anesthetized with either fentanyl/fluanisone/midazolam or urethane. No significant differences in the volume of distribution of gentamicin were observed between any of the groups studied, either anesthetized or conscious. Carboxyinulin blood clearance in the conscious group was significantly higher than that with urethane, fentanyl/fluanisone/midazolam, pentobarbitone, or ketamine/midazolam but not significantly different from alphaxolone/ alphadolone-anesthetized animals. The differences in carboxyinulin clearance were noted to be proportional to the differences in gentamicin clearance (r 2 = 0.98). These results demonstrate that the choice of anesthetic used in laboratory pharmacokinetic studies is important. Gentamicin clearance was higher in conscious than anesthetized rats, and it may be prudent to use chronically catheterized animals in pharmacokinetic studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015879324354
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 189
    Electronic Resource
    Electronic Resource
    The Effects of Urine pH Modification on the Pharmacokinetics and Pharmacodynamics of Phenylpropanolamine (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 96-102 
    Details
    ISSN: 1573-904X
    Keywords: phenylpropanolamine ; urinary pH modification ; urine alkalinization ; renal clearance ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract To determine whether uninary alkalinization had an effect on the plasma pharmacokinetics and pharmacodynamics of phenylpropanolamine, a double-blind crossover study was conducted in four healthy, normotensive male volunteers. The subjects received 25 mg immediate-release phenylpropanolamine and either placebo or sodium bicarbonate in a balanced randomized order. The bicarbonate treatment consisted of 6 g sodium bicarbonate 30 min prior to the phenylpropanolamine and then 3 g sodium bicarbonate every 4 hr for the next 16 hr. During the control treatment, phenylpropanolamine and a placebo for bicarbonate (lactose) were given on the same schedule. Blood and urine samples were collected over 24 hr and analyzed by HPLC. A supine blood pressure and pulse were obtained before each blood sample. The bicarbonate treatment significantly increased the urine pH throughout the study period and decreased phenylpropanolamine renal clearance by 33.5%. The apparent total-body clearance was also decreased by 31.5% and resulted in higher postabsorptive plasma phenylpropanolamine concentrations in each subject as compared to the control treatment. Both systolic and diastolic blood pressures changed significantly from baseline in both treatments. The bicarbonate treatment was accompanied by significantly higher diastolic blood pressures than in the control treatment, but there was no effect on systolic blood pressures. Generally, when the blood pressure–concentration pairs were plotted chronologically, clockwise hysteresis curves resulted. Heart rates did not change significantly from baseline values for either treatment. In this small group of normotensive healthy male volunteers, urinary alkalinization significantly depressed the renal clearance of phenylpropanolamine, producing higher postabsorptive phenylpropanolamine plasma concentrations and a small but significant increase in the diastolic blood pressure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015852012968
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 190
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of Methylergometrine in the Rat: Evidence for Enterohepatic Recirculation by a Linked-Rat Model (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 14-20 
    Details
    ISSN: 1573-904X
    Keywords: methylergometrine ; pharmacokinetics ; rat ; enterohepatic recirculation ; protein binding ; volume of distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of methylergometrine were investigated in the rat, with emphasis on the role of biliary excretion and enterohepatic recirculation in the overall disposition of the drug. A linked-rat model, where the bile from a rat receiving a constant rate of iv infusion of methylergometrine was allowed to flow into the duodenum of another rat, was used for the estimation of the degree of enterohepatic recirculation (EHC). The excretion of unchanged methylergometrine in the bile was estimated separately. Plasma protein binding and plasma-to-whole blood partitioning were also determined. Plasma clearance in control rats was 17.4 ± 0.7 ml/min × kg for iv bolus and 15.4 ± 0.7 ml/min × kg for iv infusion. The corresponding values in the bile-cannulated rats were significantly lower, 7.7 ± 0.4 and 8.7 ± 0.1 ml/min × kg, respectively. The lower clearance in the bile-cannulated rats was caused mainly by a lower free fraction in plasma, f u (0.11 ± 0.01), in this group compared with the control group (0.19 ± 0.0.03). The unbound volume of distribution at steady state (V ssu) was only 6.5 liters/kg in the bile-cannulated rats, compared to 14.7 liters/kg in control rats, suggesting that under steady-state conditions, more than 50% of the methylergometrine is conjugated or resides in the hepatobiliary loop, either as a conjugate or unchanged. The fraction of unchanged methylergometrine excreted in the bile was less than 0.3% of the given dose, while the fraction of the dose being reabsorbed during one cycle (f reabs) was 8.4 ± 6.3%. Thus, recirculation is due mainly to excretion of conjugates subsequently hydrolzyed in the GI tract prior to absorption. In spite of this relatively low degree of EHC, the terminal half-life was reduced from 186 ± 22 min in control rats to 79 ± 5 min in rats with an interrupted EHC. The data presented emphasize the role of enterohepatic recirculation in the disposition of a drug, i.e., even if the extent of EHC is relatively low, it may markedly effect the apparent volume of distribution, hence the terminal half-life of a drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015871122537
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 191
    Electronic Resource
    Electronic Resource
    Mean Residence Times of Multicompartmental Drugs Undergoing Reversible Metabolism (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 103-107 
    Details
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; moment analysis ; reversible metabolism ; mean residence times
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015804129806
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 192
    Electronic Resource
    Electronic Resource
    Disposition of Bismuth in the Rat. II. Pharmacokinetics and Biliary Excretion (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 237-241 
    Details
    ISSN: 1573-904X
    Keywords: bismuth ; pharmacokinetics ; biliary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and biliary excretion profile of intravenously administered bismuth ions were investigated in male Sprague Dawley rats. The data indicated that in the dose range studied, the percentage of dose excreted in urine ranged from 58 to 63%. The mean residence time for bismuth ions was 3.93, 4.07, and 5.45 hr for the 0.5, 0.75, and 1.0 mg/kg dose, respectively, while the volume of distribution at steady state was 0.75, 1.24, and 1.38 L/kg for the three doses. Blood clearance values ranged from 0.2 to 0.32 L/hr/kg. Blood bismuth ion concentrations toward the latter part of the sampling schedule indicated significant variability. The bile-to-blood concentration ratio of intravenously administered bismuth exceeded 1.0 for the three doses studied, suggesting that transport of bismuth from blood to bile may be carrier mediated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015813826597
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 193
    Electronic Resource
    Electronic Resource
    Single- vs Multiple-Dose Pharmacokinetics of Clozapine in Psychiatric Patients (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 347-351 
    Details
    ISSN: 1573-904X
    Keywords: clozapine ; pharmacokinetics ; single- vs multiple-dose regimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose–multiple dose–single dose). Each patient received a single 75-mg dose (3 × 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t $$_{{\raise0.5ex\hbox{$\scriptstyle 1$}\kern-0.1em/\kern-0.15em\lower0.25ex\hbox{$\scriptstyle 2$}}} $$ m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P 〈 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402–405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis–Menten kinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015859103824
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 194
    Electronic Resource
    Electronic Resource
    Altered Pharmacokinetics and Dynamics of Apomorphine in the Malnourished Rat: Modeling of the Composed Relationship Between Concentration and Heart-Rate Response (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 318-324 
    Details
    ISSN: 1573-904X
    Keywords: apomorphine ; pharmacokinetics ; pharmacodynamics ; heart rate ; rat ; malnutrition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The impact of malnutrition on the pharmacokinetics and pharmacodynamics (change in heart rate) of apomorphine was studied in the rat. One group of rats received a low-protein diet (0.5%) ad libitum to produce prekwashiorkor. The control group received commercial food pellets. In the first experiment, the two groups received a 2 mg/kg iv bolus dose of apomorphine to determine any differences in the basic pharmacokinetic parameters. The pharmacodynamic characteristics in each group were studied at different steady-state plasma levels, achieved by iv infusions with continuous measurements of the heart rate. There was an almost twofold decrease in the plasma clearance in the malnourished rats compared with controls. A pronounced change in the pharmacodynamic response was also observed in the malnourished group. In the control group, apomorphine produced bradycardia at low concentrations and tachycardia at high concentrations, while only bradycardia was registered in the malnourished group, with maximum effects at steady-state plasma concentrations of 50 ng/ml and a return to baseline at higher concentrations. The effects in control and malnourished rats were fitted simultaneously to the sum of two Hill equations with a nonlinear regression program, and the fits were compared by means of an F test. The maximum pure tachycardia obtainable differed significantly in the prekwashiorkor group compared to the control group. These results suggest a selective down regulation/desensitization only of the receptors responsible for the tachycardia produced by apomorphine during malnutrition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015850802006
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 195
    Electronic Resource
    Electronic Resource
    Relationships in the Structure–Tissue Distribution of Basic Drugs in the Rabbit (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 691-696 
    Details
    ISSN: 1573-904X
    Keywords: basic drugs ; tissue distribution ; lipophilicity ; rabbits ; distribution of nonionized drug ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The relationship between the tissue-to-plasma partition coefficients (K p) and drug lipophilicity was investigated using highly lipophilic drugs with apparent partition coefficients of 150 or above in an octanol–water system at pH 7.4. Ten clinically popular basic drugs with different dissociation coefficients (pK a) and lipophilicity were used. The K p values were determined in nondisposing organs after the i.v. administration of individual drugs in rabbits. The free fraction in plasma and the blood-to-plasma concentration ratio were determined in vitro. Then the tissue-to-plasma ratios of nonionized and unbound drug concentrations (K pfu) were calculated from K pf (ratio of unbound drug). The true octanol–water partition coefficient of the nonionized drugs (P) was used to analyze the K pf and K pfu. In all tissues, log K pfu was more highly correlated with log P than log K pf.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015803202857
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 196
    Electronic Resource
    Electronic Resource
    A Redox-Based System that Enhances Delivery of Estradiol to the Brain: Pharmacokinetic Evaluation in the Dog (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 879-883 
    Details
    ISSN: 1573-904X
    Keywords: estradiol ; chemical delivery system ; brain enhanced drug delivery ; blood–brain barrier ; pharmacokinetics ; redox drug delivery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of a dihydropyridine–pyridinium salt-type chemical delivery system (CDS) for brain-targeted delivery of estradiol (E2) were examined in dogs. Parameters evaluated in vitro included stability in buffers and biological fluids and plasma protein binding. In vivo studies examined drug and metabolite concentrations in plasma, urine, and cerebrospinal fluid as well as in selected brain regions. The administered lipophilic E2-CDS disappeared very quickly from plasma and was not detected in urine. The oxidized drug form, E2-Q+, was excreted unchanged or as a conjugate in the urine for as long as 2 weeks. Plasma levels were below assay detection limits at later times. Pharmacokinetic analysis of urine E2-Q+ levels allowed estimation of a half-life of 2.2 days. Amounts of E2-Q+ excreted into the urine were proportional to the dose but averaged only 13.9% of the dose, indicating that other routes of excretion must be considered. CSF levels were below the limit of detection for both E2-CDS and E2-Q+, however, brain tissue concentrations of E2-Q+ were similar in several brain regions of individual animals examined 1 or 3 days after drug dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015977319212
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 197
    Electronic Resource
    Electronic Resource
    Performance of Diltiazem Tablet and Multiparticulate Osmotic Formulations in the Dog (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 874-878 
    Details
    ISSN: 1573-904X
    Keywords: diltiazem ; controlled release ; deconvolution ; dog ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The in vivo performance of two extended-release (ER) osmotic formulations of diltiazem were evaluated in the beagle dog. Both ER formulations had similar bioavailabilities (F) as the diltiazem solution. Although F was somewhat variable following ER administration, this variability may be related to the drug entity since intra- and interanimal variability of orally administered diltiazem solutions was substantial. Deconvolution of the ER plasma diltiazem data with absorption data from the orally administered diltiazem solutions provided an estimate of the in vivo drug release from the ER formulations. The two ER formulations, designed with different in vitro release profiles, reflected these differences in vivo, with nearly identical respective in vivo and in vitro release profiles.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015925302374
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 198
    Electronic Resource
    Electronic Resource
    Comparison of Single-Dose and Steady-State Nadolol Plasma Concentrations (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 953-956 
    Details
    ISSN: 1573-904X
    Keywords: nadolol ; pharmacokinetics ; high-performance liquid chromatography (HPLC) ; nonlinearity ; β-blocker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of nadolol have been previously reported to be linear between single and steady-state dosing. Data from a study in our laboratory suggested greater than expected β-blockade with nadolol at steady state. Because the early potency studies were single-dose studies, we hypothesized there was a nonlinearity in nadolol pharmacokinetics which produced higher than expected plasma concentrations at steady state. Six normal volunteers from the previous study (steady state) volunteered to participate in the single-dose study. Plasma concentrations were determined for 24 hr following a single dose of nadolol, 80 mg. A simple, inexpensive, and accurate method for determination of nadolol in plasma or serum by HPLC with fluorometric detection is described. The AUCo–tau at steady state was greater than the AUC0–∞ following a single dose in five of the six subjects. The mean ratio of AUCss/AUCsd was 2.54. This value would be unity in the presence of linear pharmacokinetics. We conclude that the principle of superposition is not applicable for nadolol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015954108734
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 199
    Electronic Resource
    Electronic Resource
    Fast inferential adaptive optimization of a continuous yeast culture based on carbon dioxide evolution rate (1990)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 35 (1990), S. 8-14 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A fast inferential, multivariable adaptive optimization algorithm based on a fast responding off-gas data, the carbon dioxide evolution rate (CER), has been developed and applied to a continuous baker's yeast culture to maximize the cellular productivity in simulation and experimental studies. In the simulation study the process was optimized based on CER measurements using readily available steady-state data on the ratio between the cellular productivity and the CER. It was shown that the algorithm is two to three times faster than the algorithm based on cell mass concentration measurements. In the experimental study the CER was maximized without any information on the relationship between the cellular productivity and the CER. It took about 40 h for the process to converge, while about 80 h was required when the optimization was based on cell mass measurements. The attained steady state was found to be different but fairly close to that obtained with cell measurements. Briefly discussed is a switching to the cell-mass-based algorithm at the final stage of the optimization to overcome a potential inaccuracy.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260350103
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 200
    Electronic Resource
    Electronic Resource
    Oxygen transfer rates in a mammalian cell culture bioreactor equipped with a cell-lift impeller (1990)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 35 (1990), S. 43-49 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Measurements of kLa were carried out in 1. 5- and 5-L New Brunswick Scientific CelliGen® bioreactors. The measured kLa in water were identical for both vessel sizes operated in similar condition. The mass transfer rate increased with temperature, mixing speed, and aeration rate, with this last parameter being the most significant. Surface aeration alone gave kLa values of 0. 4 to 1. 6 h-1. A 25% decrease in kLa was observed above an aeration rate of 1. 6 vvm. This was caused by the particular foam breaker of the CelliGen bioreactor. Measurements of kLa using a mammalian cell culture medium supplemented with 5% fetal calf serum (FCS) have confirmed the negative effect of the foam breaker on kLa The measured value in this medium was 1. 2 h-1 for all aeration rates, more than 60% of which was attributed to surface aeration.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260350107
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...