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Substrate and stereochemical control of peptidoglycan cross-linking by transpeptidation by Escherichia coli PBP1B
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Catherwood, Anita C., Lloyd, Adrian J., Tod, Julie A., Chauhan, Smita, Slade, Susan E., Walkowiak, Grzegorz P., Galley, Nicola F., Punekar, Avinash S., Smart, Katie, Rea, Dean, Evans, Neil D., Chappell, Michael J., Roper, David I. and Dowson, Christopher G. (2020) Substrate and stereochemical control of peptidoglycan cross-linking by transpeptidation by Escherichia coli PBP1B. Journal of the American Chemical Society, 142 (11). pp. 5034-5048. doi:10.1021/jacs.9b08822
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WRAP-substrate-stereochemical-control-peptidoglycan-cross-linking-transpeptidation-Escherichia-coli-PBP1B-Dowson-2020.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only until 12 February 2021. Contact author directly, specifying your specific needs. - Requires a PDF viewer. Download (2593Kb) |
Official URL: http://dx.doi.org/10.1021/jacs.9b08822
Abstract
Penicillin binding proteins (PBPs) catalyzing transpeptidation reactions that stabilize the peptidoglycan component of the bacterial cell wall are the targets of β-lactams, the most clinically successful antibiotics to date. However, PBP-transpeptidation enzymology has evaded detailed analysis, because of the historical unavailability of kinetically competent assays with physiologically relevant substrates and the previously unappreciated contribution of protein cofactors to PBP activity. By re-engineering peptidoglycan synthesis, we have constructed a continuous spectrophotometric assay for transpeptidation of native or near native peptidoglycan precursors and fragments by Escherichia coli PBP1B, allowing us to (a) identify recognition elements of transpeptidase substrates, (b) reveal a novel mechanism of stereochemical editing within peptidoglycan transpeptidation, (c) assess the impact of peptidoglycan substrates on β-lactam targeting of transpeptidation, and (d) demonstrate that both substrates have to be bound before transpeptidation occurs. The results allow characterization of high molecular weight PBPs as enzymes and not merely the targets of β-lactam acylation.
| Item Type: | Journal Article | ||||||||||||
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| Subjects: | Q Science > QP Physiology Q Science > QR Microbiology |
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| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||||||||||
| Library of Congress Subject Headings (LCSH): | Drug resistance in microorganisms, Bacterial cell walls, Peptidoglycans, Escherichia coli, Transpeptidation | ||||||||||||
| Journal or Publication Title: | Journal of the American Chemical Society | ||||||||||||
| Publisher: | American Chemical Society | ||||||||||||
| ISSN: | 0002-7863 | ||||||||||||
| Official Date: | 18 March 2020 | ||||||||||||
| Dates: |
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| Date of first compliant deposit: | 7 April 2020 | ||||||||||||
| Volume: | 142 | ||||||||||||
| Number: | 11 | ||||||||||||
| Page Range: | pp. 5034-5048 | ||||||||||||
| DOI: | 10.1021/jacs.9b08822 | ||||||||||||
| Status: | Peer Reviewed | ||||||||||||
| Publication Status: | Published | ||||||||||||
| Publisher Statement: | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jacs.9b08822 | ||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||||||
| RIOXX Funder/Project Grant: |
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