Monitoring conformational changes in the NDM-1 metallo-β-lactamase by 19F NMR spectroscopy.
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 ace...
| Հիմնական հեղինակներ: | , , , , , , |
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| Ձևաչափ: | Journal article |
| Լեզու: | English |
| Հրապարակվել է: |
Wiley
2014
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| _version_ | 1826300244060536832 |
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| author | Rydzik, A Brem, J van Berkel, S Pfeffer, I Makena, A Claridge, T Schofield, C |
| author_facet | Rydzik, A Brem, J van Berkel, S Pfeffer, I Makena, A Claridge, T Schofield, C |
| author_sort | Rydzik, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:14:13Z |
| format | Journal article |
| id | oxford-uuid:dc9a3d57-4967-4f40-a35c-0e3e79bae70a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:14:13Z |
| publishDate | 2014 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:dc9a3d57-4967-4f40-a35c-0e3e79bae70a2022-03-27T09:18:51ZMonitoring conformational changes in the NDM-1 metallo-β-lactamase by 19F NMR spectroscopy.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dc9a3d57-4967-4f40-a35c-0e3e79bae70aEnglishSymplectic Elements at OxfordWiley2014Rydzik, ABrem, Jvan Berkel, SPfeffer, IMakena, AClaridge, TSchofield, CThe 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. |
| spellingShingle | Rydzik, A Brem, J van Berkel, S Pfeffer, I Makena, A Claridge, T Schofield, C Monitoring conformational changes in the NDM-1 metallo-β-lactamase by 19F NMR spectroscopy. |
| title | Monitoring conformational changes in the NDM-1 metallo-β-lactamase by 19F NMR spectroscopy. |
| title_full | Monitoring conformational changes in the NDM-1 metallo-β-lactamase by 19F NMR spectroscopy. |
| title_fullStr | Monitoring conformational changes in the NDM-1 metallo-β-lactamase by 19F NMR spectroscopy. |
| title_full_unstemmed | Monitoring conformational changes in the NDM-1 metallo-β-lactamase by 19F NMR spectroscopy. |
| title_short | Monitoring conformational changes in the NDM-1 metallo-β-lactamase by 19F NMR spectroscopy. |
| title_sort | monitoring conformational changes in the ndm 1 metallo β lactamase by 19f nmr spectroscopy |
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