Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

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 ISSN 0002-7863.

[img]
Preview
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

Request Changes to record.

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, Engineering and Medicine > 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:
DateEvent
18 March 2020Published
12 February 2020Available
12 February 2020Accepted
Volume: 142
Number: 11
Page Range: pp. 5034-5048
DOI: 10.1021/jacs.9b08822
Status: Peer Reviewed
Publication Status: Published
Reuse Statement (publisher, data, author rights): 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
Date of first compliant deposit: 7 April 2020
Date of first compliant Open Access: 12 February 2021
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
BB/K017268/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
MR/N014294/[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
BB/N003241/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us