The Library
Substrate and stereochemical control of peptidoglycan cross-linking by transpeptidation by Escherichia coli PBP1B
Tools
Tools
Tools
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
|
PDF
WRAP-substrate-stereochemical-control-peptidoglycan-cross-linking-transpeptidation-Escherichia-coli-PBP1B-Dowson-2020.pdf - Accepted Version - Requires a PDF viewer. Download (2593Kb) | Preview |
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 | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QP Physiology Q Science > QR Microbiology |
||||||||||||
| 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: |
|
||||||||||||
| 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: |
|
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
