Monitoring Conformational Changes in the NDM-1 Metallo-β-lactamase by 19F NMR Spectroscopy**

نویسندگان

  • Anna M Rydzik
  • Jürgen Brem
  • Sander S van Berkel
  • Inga Pfeffer
  • Anne Makena
  • Timothy D W Claridge
  • Christopher J Schofield
چکیده

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.

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عنوان ژورنال:

دوره 53  شماره 

صفحات  -

تاریخ انتشار 2014