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Analysis of β-lactone formation by clinically observed carbapenemases informs on a novel antibiotic resistance mechanism

Abstract:

An important mechanism of resistance to β-lactam antibiotics is via their β-lactamase–catalyzed hydrolysis. Recent work has shown that, in addition to the established hydrolysis products, the reaction of the class D nucleophilic serine β-lactamases (SBLs) with carbapenems also produces β-lactones. We report studies on the factors determining β-lactone formation by class D SBLs. We show that variations in hydrophobic residues at the active site of class D SBLs (i.e. Trp105, Val120, and Leu158,...

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Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1074/jbc.RA120.014607

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Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Organic Chemistry
Role:
Author
ORCID:
0000-0002-0290-6565
More from this funder
Name:
Wellcome Trust
Grant:
106244/Z/14/Z
More from this funder
Name:
European Commission
Grant:
115583
More from this funder
Name:
Medical Research Council
Grant:
MR/T016035/1
Publisher:
American Society for Biochemistry and Molecular Biology
Journal:
Journal of Biological Chemistry More from this journal
Volume:
295
Issue:
49
Pages:
16604-16613
Publication date:
2020-09-22
Acceptance date:
2020-09-22
DOI:
EISSN:
1083-351X
ISSN:
0021-9258
Language:
English
Keywords:
Pubs id:
1133290
Local pid:
pubs:1133290
Deposit date:
2020-09-23

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