Issue 2, 2015

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

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.

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

Supplementary files

Article information

Article type
Edge Article
Submitted
12 jun 2014
Accepted
24 out 2014
First published
24 out 2014
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2015,6, 956-963

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

J. Brem, W. B. Struwe, A. M. Rydzik, H. Tarhonskaya, I. Pfeffer, E. Flashman, S. S. van Berkel, J. Spencer, T. D. W. Claridge, M. A. McDonough, J. L. P. Benesch and C. J. Schofield, Chem. Sci., 2015, 6, 956 DOI: 10.1039/C4SC01752H

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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