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| Content Provider | PubMed Central |
|---|---|
| Author | Karsisiotis, Andreas Ioannis Damblon, Christian F. Roberts, Gordon C. K. |
| Copyright Year | 2013 |
| 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. In the present study 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. |
| Related Links | http://dx.doi.org/10.1042/bj20131003 |
| Ending Page | 407 |
| Page Count | 11 |
| Starting Page | 397 |
| File Format | |
| ISSN | 02646021 |
| e-ISSN | 14708728 |
| Journal | Biochemical Journal |
| Issue Number | Pt 3 |
| Volume Number | 456 |
| Language | English |
| Publisher | Portland Press Ltd. |
| Publisher Date | 2013-12-15 |
| Access Restriction | Open |
| Rights Holder | Portland Press Ltd. |
| Subject Keyword | Cell Biology Biochemistry Molecular Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology Biochemistry |
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