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Journal article

A new mechanism for β-lactamases: Class D enzymes degrade 1β-methyl carbapenems through lactone formation

Abstract:

β-Lactamases threaten the clinical use of carbapenems, which are considered antibiotics of last resort. The classical mechanism of serine carbapenemase catalysis proceeds through hydrolysis of an acyl-enzyme intermediate. We show that class D β-lactamases also degrade clinically used 1β-methyl-substituted carbapenems through the unprecedented formation of a carbapenem-derived β-lactone. β-Lactone formation results from nucleophilic attack of the carbapenem hydroxyethyl side chain on the ester...

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Publication status:
Published
Peer review status:
Peer reviewed
Version:
Publisher's version

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Publisher copy:
10.1002/anie.201711308

Authors


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Institution:
University of Oxford
Division:
MPLS Division
Department:
Chemistry
Role:
Author
ORCID:
0000-0003-1094-0349
More by this author
Institution:
University of Oxford
Division:
MPLS Division
Department:
Chemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS Division
Department:
Chemistry
Role:
Author
ORCID:
0000-0002-5615-6237
More by this author
Institution:
University of Oxford
Division:
MPLS Division
Department:
Chemistry
Role:
Author
ORCID:
0000-0003-2180-3235
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Publisher:
Wiley Publisher's website
Journal:
Angewandte Chemie International Edition Journal website
Volume:
57
Issue:
5
Pages:
1282-1285
Publication date:
2018-01-05
Acceptance date:
2017-12-13
DOI:
EISSN:
1521-3773
ISSN:
1433-7851
Pubs id:
pubs:811183
URN:
uri:abc26748-d457-482c-8535-6c2670b04fea
UUID:
uuid:abc26748-d457-482c-8535-6c2670b04fea
Local pid:
pubs:811183

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