Monitoring Conformational Changes in the NDM‐1 Metallo‐β‐lactamase by 19F NMR Spectroscopy |
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| Authors: | Anna M. Rydzik Jürgen Brem Sander S. van Berkel Inga Pfeffer Anne Makena Dr. Timothy D. W. Claridge Prof. Christopher J. Schofield |
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| Affiliation: | Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA (UK) |
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| Abstract: | The New Delhi metallo‐β‐lactamase (NDM‐1) is involved in the emerging antibiotic resistance problem. Development of metallo‐β‐lactamases (MBLs) inhibitors has proven challenging, due to their conformational flexibility. Here we report site‐selective labeling of NDM‐1 with 1,1,1‐trifluoro‐3‐bromo acetone (BFA), and its use to study binding events and conformational changes upon ligand–metal binding using 19F NMR spectroscopy. The results demonstrate different modes of binding of known NDM‐1 inhibitors, including L ‐ and D ‐captopril by monitoring the changing chemical environment of the active‐site loop of NDM‐1. The method described will be applicable to other MBLs and more generally to monitoring ligand‐induced conformational changes. |
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| Keywords: | 19F‐NMR antibiotic resistance captopril metallo‐β ‐lactamases NDM‐1 |
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