Monitoring conformational changes in the NDM-1 metallo-β-lactamase by 19F NMR spectroscopy
| Autor: | Anne Makena, Sander S. van Berkel, Jürgen Brem, Timothy D. W. Claridge, Anna M. Rydzik, Christopher J. Schofield, Inga Pfeffer |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Magnetic Resonance Spectroscopy
antibiotic resistance 19f nmr spectroscopy Stereochemistry Nanotechnology Fluorine-19 NMR NDM-1 19F-NMR 010402 general chemistry 01 natural sciences Catalysis Metallo β lactamase beta-Lactamases Molecule Molecular Structure Chemistry 010405 organic chemistry Drug Resistance Microbial General Chemistry Nuclear magnetic resonance spectroscopy General Medicine Communications 0104 chemical sciences captopril metallo-β-lactamases New delhi |
| Zdroj: | Angewandte Chemie (International Ed. in English) |
| Popis: | 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 (19) F 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. |
| Databáze: | OpenAIRE |
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