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Royal Society of Chemistry, Chemical Science, 2(6), p. 956-963

DOI: 10.1039/c4sc01752h

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Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1

Journal article published in 2015 by Jürgen Brem ORCID, Weston B. Struwe, Anna M. Rydzik, Hanna Tarhonskaya, Inga Pfeffer, Emily Flashman, Sander S. van Berkel, James Spencer, Timothy D. W. Claridge, Michael A. McDonough, Justin L. P. Benesch, Christopher J. Schofield
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Metallo-β-lactamases (MBLs) catalyse the hydrolysis of almost all β-lactam antibiotics. We report biophysical and kinetic studies on the São Paulo MBL (SPM-1), which reveal its Zn(II) ion usage and mechanism as characteristic of the clinically important di-Zn(II) dependent B1 MBL subfamily. Biophysical analyses employing crystallography, dynamic 19F NMR and ion mobility mass spectrometry, however, reveal that SPM-1 possesses loop and mobile element regions characteristic of the B2 MBLs. These include a mobile α3 region which is important in catalysis and determining inhibitor selectivity. SPM-1 thus appears to be a hybrid B1/B2 MBL. The results have implications for MBL evolution and inhibitor design.