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Title: Solution structures of the Bacillus cereus metallo-β-lactamase BcII and its complex with the broad spectrum inhibitor R-thiomandelic acid
Authors: Karsisiotis, Andreas Ioannis
Damblon, Christian F.
Roberts, Gordon C.K.
First Published: 24-Sep-2013
Publisher: Portland Press for the Biochemical Society
Citation: Biochemical Journal, 2013, 456 (3), pp. 397-407
Abstract: Metallo-β-lactamases, enzymes which inactivate β-lactam antibiotics, are of increasing biological and clinical significance as a source of antibiotic resistance in pathogenic bacteria. We describe the high resolution solution NMR structures of the Bacillus cereus metallo-β-lactamase, BcII, and of its complex with R-thiomandelic acid, a broad spectrum inhibitor of metallo-β-lactamases. This is the first reported solution structure of any metallo-β-lactamase. There are differences between the solution structure of the free enzyme and previously reported crystal structures in the loops flanking the active site, which are important for substrate and inhibitor binding and catalysis. The binding of R-thiomandelic acid and the roles of active site residues are defined in detail. Changes in the enzyme structure upon inhibitor binding clarify the role of the mobile β3-β4 loop. Comparisons with other metallo-β-lactamases highlight the roles of individual amino-acid residues in the active site and the β3-β4 loop in inhibitor binding and provide information on the basis of structure-activity relationships among metallo-β-lactamase inhibitors.
DOI Link: 10.1042/BJ20131003
ISSN: 0264-6021
eISSN: 1470-8728
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2013 The Author(s). This article is published under the terms of the Creative Commons Attribution Licence (CC-BY) ( which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.
Appears in Collections:Published Articles, Dept. of Biochemistry

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