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19F-NMR reveals the role of mobile loops in product and inhibitor binding by the São Paulo metallo-β-lactamase

Abstract:

Resistance to beta-lactam antibiotics mediated by metallo-beta-lactamases (MBLs) is a growing problem. We describe the use of protein-observe 19F-NMR (PrOF NMR) to study the dynamics of the São Paulo MBL (SPM-1) from beta-lactam- resistant Pseudomonas aeruginosa. Cysteinyl variants on the a3 and L3 regions, which flank the di-ZnII active site, were selectively 19F-labeled using 3-bromo-1,1,1-trifluoroacetone. The PrOF NMR results reveal roles for the mobile a3 and L3 regions in the binding of...

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Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1002/anie.201612185

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Department:
Oxford, MPLS, Chemistry, Chemical Biology
Hinchliffe, P More by this author
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Department:
Oxford, MPLS, Chemistry, Organic Chemistry
Pfeffer, I More by this author
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Rhodes Scholarship More from this funder
Wellcome Trust More from this funder
SWON Alliance More from this funder
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Publisher:
Wiley Publisher's website
Journal:
Angewandte Chemie International Edition Journal website
Publication date:
2017-03-05
Acceptance date:
2017-01-16
DOI:
ISSN:
1521-3757
Pubs id:
pubs:684155
URN:
uri:bab1de9e-ed5e-4c4d-91fe-63b02ebced91
UUID:
uuid:bab1de9e-ed5e-4c4d-91fe-63b02ebced91
Local pid:
pubs:684155

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