Monitoring Conformational Changes in the NDM‐1 Metallo‐β‐lactamase by 19F NMR Spectroscopy1. (24th February 2014)

• Record Type: Journal Article
• Authors: Rydzik, Anna M.; Brem, Jürgen; van Berkel, Sander S.; Pfeffer, Inga; Makena, Anne; Claridge, Timothy D. W.; Schofield, Christopher J.
• Is Part Of: Angewandte Chemie. Volume 126:Number 12(2014)
• Page Start: 3193
• Page End: 3197
• Publication Date: 2014-02-24
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201310866
• Languages: English
• ISSNs: 0044-8249

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 <italic><sc>L</sc></italic>‐ and <italic><sc>D</sc></italic>‐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.</p> </abstract>