ZIB

Hits per page

hits 1 - 2 | 2 hits

Sorting

Electronic Resource

Inhibition of IMP-1 metallo-β-lactamase and sensitization of IMP-1-producing bacteria by thioester derivatives (1999)

Hammond, Gail G. ; Huber, Joann L. ; Greenlee, Mark L. ; [et al.]

Oxford, UK : Blackwell Publishing Ltd

FEMS microbiology letters 179 (1999), S. 0

add to mindlist on the mindlist

Details

ISSN: 1574-6968

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Biology

Notes: IMP-1 metallo-β-lactamase is a transferable carbapenem-hydrolyzing enzyme found in some clinical isolates of Pseudomonas aeruginosa, Serratia marcescens and Klebsiella pneumoniae. Bacteria that express IMP-1 show significantly reduced sensitivity to carbapenems and other β-lactam antibiotics. A series of thioester derivatives has been shown to competitively inhibit purified IMP-1. As substrates for IMP-1, the thioesters yielded thiol hydrolysis products which themselves were reversible competitive inhibitors. The thioesters also increased sensitivity to the carbapenem L-742,728 in an IMP-1-producing laboratory stain of Escherichia coli, but will need further modification to improve their activity in less permeable organisms such as Pseudomonas and Serratia. Nonetheless, the thioester IMP-1 inhibitors offer an encouraging start to overcoming metallo-β-lactamase-mediated resistance in bacteria.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1111/j.1574-6968.1999.tb08740.x

Permalink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

Electronic Resource

A high quality nuclear magnetic resonance solution structure of peptide deformylase from Escherichia coli: Application of an automated assignment strategy using GARANT (1999)

O'Connell, John F. ; Pryor, KellyAnn D. ; Grant, Stephan K. ; [et al.]

Springer

Journal of biomolecular NMR 13 (1999), S. 311-324

add to mindlist on the mindlist

Details

ISSN: 1573-5001

Keywords: automated assignment ; distance geometry ; peptide deformylase ; protein structure ; structure refinement

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Chemistry and Pharmacology

Notes: Abstract The NMR structure of the peptide deformylase (PDF) (1–150) from Escherichia coli, which is an essential enzyme that removes the formyl group from nascent polypeptides and represents a potential target for drug discovery, was determined using 15N/13C doubly labeled protein. Nearly completely automated assignment routines were employed to assign three-dimensional triple resonance, 15N-resolved and 13C-resolved NOESY spectra using the program GARANT. This assignment strategy, demonstrated on a 17 kDa protein, is a significant advance in the automation of NMR data assignment and structure determination that will accelerate future work. A total of 2302 conformational constraints were collected as input for the distance geometry program DYANA. After restrained energy minimization with the program X-PLOR the 20 best conformers characterize a high quality structure with an average of 0.43 Å for the root-mean-square deviation calculated from the backbone atoms N, Cα and C′, and 0.81 Å for all heavy atoms of the individual conformers relative to the mean coordinates for residues 1 to 150. The globular fold of PDF contains two α-helices comprising residues 25–40, 125–138, six β-strands 57–60, 70–77, 85–88, 98–101, 105–111, 117–123 and one 310 helix comprising residues 49–51. The C-terminal helix contains the HEXXH motif positioning a zinc ligand in a similar fashion to other metalloproteases, with the third ligand being cysteine and the fourth presumably a water. The three-dimensional structure of PDF affords insight into the substrate recognition and specificity for N-formylated over N-acetylated substrates and is compared to other PDF structures.