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Issue 2, 2015
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Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1

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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.

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

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Publication details

The article was received on 12 Jun 2014, accepted on 24 Oct 2014 and first published on 24 Oct 2014


Article type: Edge Article
DOI: 10.1039/C4SC01752H
Chem. Sci., 2015,6, 956-963
  • Open access: Creative Commons BY license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    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

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