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13 C-Carbamylation as a mechanistic probe for the inhibition of class D β-lactamases by avibactam and halide ions

Abstract:

The class D (OXA) serine β-lactamases are a major cause of resistance to β-lactam antibiotics. The class D enzymes are unique amongst β-lactamases because they have a carbamylated lysine that acts as a general acid/base in catalysis. Previous crystallographic studies led to the proposal that β-lactamase inhibitor avibactam targets OXA enzymes in part by promoting decarbamylation. Similarly, halide ions are proposed to inhibit OXA enzymes via decarbamylation. NMR analyses, in which the carbamy...

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Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1039/C7OB01514C

Authors


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Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Organic Chemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Organic Chemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Organic Chemistry
Role:
Author
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Grant:
MRC/ Canadian Grant G1100135,
AstraZeneca More from this funder
Publisher:
Royal Society of Chemistry Publisher's website
Journal:
Organic and Biomolecular Chemistry Journal website
Volume:
15
Issue:
28
Pages:
6024-6032
Publication date:
2017-06-26
Acceptance date:
2017-06-26
DOI:
EISSN:
1477-0539
ISSN:
1477-0520
Source identifiers:
703028
Pubs id:
pubs:703028
UUID:
uuid:6300cd93-8b87-4223-99f5-41b08a1e9296
Local pid:
pubs:703028
Deposit date:
2017-07-05

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