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  • Electronic Resource  (25)
  • 1995-1999  (23)
  • 1930-1934  (2)
  • Biochemistry and Biotechnology  (22)
  • Inorganic Chemistry
  • 1
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 130 (1997), S. 669-681 
    ISSN: 0009-2940
    Keywords: Bismuth ; Metallodrugs ; Bioinorganic chemistry ; Chelates ; Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Bismuth compounds have been widely used in medicine for more than 200 years, and new bismuth-containing drugs are now being developed. However the biological chemistry of bismuth is poorly understood. We review here methods for the study of bismuth compounds, and use of Bi(III) in antiulcer, antibacterial, anti-HIV and radiotherapeutic agents is described. The chemistry of Bi(III) carboxylates and aminocarboxylates is dominated by intermolecular interactions which lead to polymeric structures. Bi(III) exhibits a highly variable coordination number and coordination geometry, and alkoxide ligands can induce a strong stereochemical “lone-pair effect”. Bi(III) can bind to both Zn(II) sites (e.g. metallothionein) and Fe(III) sites (e.g. transferrin) in proteins. Further work is needed to understand the relationship between the structures and dynamics of bismuth compounds and their bioactivity.
    Additional Material: 10 Ill.
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  • 2
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 56 (1997), S. 9-22 
    ISSN: 0006-3592
    Keywords: condensation reactions ; disaccharides ; equilibria ; glucoamylase ; kinetics ; monosaccharides ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Arabinose, fructose, galactose, myo-inositol, lyxose, mannose, ribose, and xylose were incubated individually and with glucose in the presence of Aspergillus niger glucoamylase at pH 4.5 and 45°C. Glucoamylase condenses galactose, glucose, and mannose individually into disaccharides. It also produces mixed disaccharides when each of the eight carbohydrates is incubated with glucose. Many products were identified by gas chromatography of the derivatized reaction mixtures followed by mass spectroscopy of the individual chromatographic peaks. Galacto-, gluco-, or mannopyranosyl rings appear to be present at the nonreducing ends of all the disaccharides produced. Molecules linked through primary hydroxyl groups have the highest equilibrium constants of all products formed, since these bonds are thermodynamically favored. However, glucoamylase is capable of forming bonds with many available hydroxyl groups, as previously demonstrated when it was incubated with glucose alone. Formation rates of different bonds linking different residues vary widely. These results demonstrate that glucoamylase has a wide selectivity toward residues it will condense into disaccharides and toward bonds it will form between them. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 9-22, 1997.
    Additional Material: 2 Ill.
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  • 3
    ISSN: 0887-3585
    Keywords: de novo design ; protein structure ; inverse folding ; genetic algorithms ; 1H NMR ; CD ; peptide ; protein folding ; methanol ; ethylene glycol ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: In response to the Paracelsus Challenge (Rose and Creamer, Proteins, 19:1-3, 1994), we present here the design, synthesis, and characterization of a helical protein, whose sequence is 50% identical to that of an all-β protein. The new sequence was derived by applying an inverse protein folding approach, in which the sequence was optimized to “fit” the new helical structure, but constrained to retain 50% of the original amino acid residues. The program utilizes a genetic algorithm to optimize the sequence, together with empirical potentials of mean force to evaluate the sequence-structure compatibility. Although the designed sequence has little ordered (secondary) structure in water, circular dichroism and nuclear magnetic resonance data show clear evidence for significant helical content in water/ethylene glycol and in water/methanol mixtures at low temperatures, as well as melting behavior indicative of cooperative folding. We believe that this represents a significant step toward meeting the Paracelsus Challenge.
    Additional Material: 5 Ill.
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 27 (1997), S. 235-248 
    ISSN: 0887-3585
    Keywords: acarviosinide ; active site ; docking ; glucoamylase ; molecular mechanics ; monosaccharides ; simulated annealing ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Glucoamylase is an important industrial glucohydrolase with a large specificity range. To investigate its interaction with the monosaccharides D-glucose, D-mannose, and D-galactose and with the substrate analogues 1-deoxynojirimycin, D-glucono-1,5-lactone, and methyl αacarviosinide, MM3(92)-optimized structures were docked into its active site using AutoDock 2.1. The results were compared to structures of glucoamylase complexes obtained by protein crystallography. Charged forms of some substrate analogues were also docked to assess the degree of protonation possessed by glucoamylase inhibitors. Many forms of methyl αa-carviosinide were conformationally mapped by using MM3(92), characterizing the conformational pH dependence found for the acarbose family of glucosidase inhibitors. Their significant conformers, representing the most common states of the inhibitor, were used as initial structures for docking. This constitutes a new approach for the exploration of binding modes of carbohydrate chains. Docking results differ slightly from x-ray crystallographic data, the difference being of the order of the crystallographic error. The estimated energetic interactions, even though agreeing in some cases with experimental binding kinetics, are only qualitative due to the large approximations made by AudoDock force field. © 1997 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 29 (1997), S. 123-128 
    ISSN: 0887-3585
    Keywords: protein structure prediction ; hidden Markov models ; fold recognition ; secondary structure ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We present an analysis of the blind predictions submitted to the fold recognition category for the second meeting on the Critical Assessment of techniques for protein Structure Prediction. Our method achieves fold recognition from predicted secondary structure sequences using hidden Markov models (HMMs) of protein folds. HMMs are trained only with experimentally derived secondary structure sequences of proteins having similar fold, therefore protein structures are described by the models at a remarkably simplified level. We submitted predictions for five target sequences, of which four were later found to be suitable for threading. Our approach correctly predicted the fold for three of them. For a fourth sequence the fold could have been correctly predicted if a better model for its structure was available. We conclude that we have additional evidence that secondary structure information represents an important factor for achieving fold recognition. Proteins, Suppl. 1:123-128, 1997. Published 1998 Wiley-Liss, Inc.This article is a US government work and, as such, is in the public domain in the United States of America.
    Additional Material: 1 Ill.
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 26 (1996), S. 217-235 
    ISSN: 0887-3585
    Keywords: catalytic region ; comparative modeling ; cysteine-rich domain ; phosphorylation ; pseudo-substrate specificity ; synaptotagmin ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Three-dimensional models of the five functional modules in human protein kinase Cα (PKCα) have been generated on the basis of known related structures. The catalytic region at the C-terminus of the sequence and the N-terminal auto-inhibitory pseudo-substrate have been modeled using the crystal structure complex of cAMP-dependent protein kinese (cAPK) and PKI peptide. While the N-terminal helix of the catalytic region of PKCα is predicted to be in a different location compared with cAPK, the C-terminal extension is modeled like that in the cAPK. The predicted permissive phosphorylation site of PKCα, Thr 497, is found to be entirely consistent with the mutagenesis studies. Basic Lys and Arg residues in the pseudo-substrate make several specific interactions with acidic residues in the catalytic region and may interact with the permissive phosphorylation site. Models of the two zinc-binding modules of PKCα are based on nuclear magnetic resonance and crystal structures of such modules in other PKC isoforms while the calcium phospholipid binding module (C2) is based on the crystal structure of a repeating unit in synaptotagmin I. Phorbol ester binding regions in zinc-binding modules and the calcium binding region in the C2 domain are similar to those in the basis structures. A hypothetical model of the relative positions of all five modules has the putative lipid binding ends of the C2 and the two zinc-binding domains pointing in the same direction and may serve as a basis for further experiments. © 1996 Wiley-Liss, Inc.
    Additional Material: 10 Ill.
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  • 7
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 28 (1997), S. 162-173 
    ISSN: 0887-3585
    Keywords: AutoDock ; cellobioside ; disaccharide ; docking ; gentiobioside ; glucoamylase ; kojibioside ; maltoside ; nigeroside ; simulated annealing ; trehalose ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: To better understand the molecular basis of glucomylase selectivity, low-energy conformers of glucosyl disaccharides obtained from relaxed-residue conformational mapping were flexibly docked into the glucoamylase active site using AutoDock 2.2. This procedure ensures that significant conformational space is searched and can produce bound structures comparable to those obtained by protein crystallography. α-Linked glucosyl disaccharides except α,α-trehalose dock easily into the active site while exclusively β-linked disaccharides do not, explaining why only the former are glucoamylase substrates. The optimized docking modes are similar at the nonreducing end of the different substrates. Individual atomic energies of intermolecular interaction allow the definite identification of key hydroxyl groups for each substrate. This approach confirmed the versatility of the second subsite of the glucoamylase active site in binding different substrates. Proteins 28:162-173, 1997. © 1997 Wiley-Liss Inc.
    Additional Material: 2 Ill.
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 29 (1997), S. 334-347 
    ISSN: 0887-3585
    Keywords: evolution ; glucoamylase ; hydrophobic folding ; protein parsimony analysis ; structure/function ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: To correlate structural features with glucoamylase properties, a structure-based multisequence alignment was constructed using information from catalytic and starch-binding domain models. The catalytic domain is composed of three hydrophobic folding units, the most labile and least hydrophobic of them being missing in the most stable glucoamylase. The role of O-glycosylation in stabilizing the most hydrophobic folding unit, the only one where thermostabilizing mutations with unchanged activity have been made, is described. Differences in both length and composition of interhelical loops are correlated with stability and selectivity characteristics. Two new glucoamylase subfamilies are defined by using homology criteria. Protein parsimony analysis suggests an ancient bacterial origin for the glucoamylase gene. Increases in length of the belt surrounding the active site, degree of O-glycosylation, and length of the linker probably correspond to evolutionary steps that increase stability and secretion levels of Aspergillus-related glucoamylases. Proteins 29:334-347, 1997. © 1997 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 32 (1998), S. 334-349 
    ISSN: 0887-3585
    Keywords: antifungal ; thionin ; NMR ; structure ; scorpion ; toxins ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The three-dimensional structure of the Sorghum bicolor seed protein γ-thionin SIα1 has been determined by 2D 1H nuclear magnetic resonance (NMR) spectroscopy. The secondary structure of this 47-residue antifungal protein with four disulphide bridges consists of a three-stranded antiparallel sheet and one helix. The helix is tethered to the sheet by two disulphide bridges which link two successive turns of the helix to alternate residues i, i + 2 in one strand. Possible binding sites for antifungal activity are discussed. The same fold has been observed previously in several scorpion toxins. Proteins 32:334-349, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 10 Ill.
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  • 10
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 59 (1998), S. 68-72 
    ISSN: 0006-3592
    Keywords: enzymatic ; solid-to-solid conversion ; peptide synthesis ; proteases ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: We have studied a thermolysin-catalyzed solid-to-solid dipeptide synthesis using equimolar amounts of Z-Gln-OH and H-Leu-NH2 as model substrates. The high substrate concentrations make this an effective alternative to enzymatic peptide synthesis in organic solvents. Water content was varied in the range of 0 to 600 mL water per mol substrate and enzyme concentration in the range of 0.5 to 10 g/mol of substrates. High yields around 80% conversion and initial rates from 5 to 20 mmol s-1 kg-1 were achieved. The initial rate increases 10-fold on reducing the water content, to reach a pronounced optimum at 40 mL water per mol substrate. Below this, the rate falls to much lower values in a system with no added water, and to zero in a rigorously dried system. This behavior is discussed in terms of two factors: At higher water contents the system is mass transfer limited (as shown by varying enzyme content), and the diffusion distances required vary. At low water levels, effects reflect the stimulation of the enzymatic activity by water. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 59:68-72, 1998.
    Additional Material: 4 Ill.
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