title: Monitoring conformational changes in the NDM-1 metallo-β-lactamase by 19F NMR spectroscopy.
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 (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.
authors.affiliation: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA (UK).
authors.forename: Anna M
authors.initials: AM
authors.lastname: Rydzik
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brem
authors.forename: Sander S
authors.initials: SS
authors.lastname: van Berkel
authors.forename: Inga
authors.initials: I
authors.lastname: Pfeffer
authors.forename: Anne
authors.initials: A
authors.lastname: Makena
authors.forename: Timothy D W
authors.initials: TD
authors.lastname: Claridge
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
mesh_terms: D004352:Drug Resistance, Microbial; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D015394:Molecular Structure; D001618:beta-Lactamases / Q000737:chemistry*
chemical_list: D001618:beta-Lactamases; C552864:beta-lactamase NDM-1
keywords: 19F-NMR; NDM-1; antibiotic resistance; captopril; metallo-β-lactamases