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

Jürgen Brem, 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

Research output: Contribution to journalArticle (Academic Journal)

26 Citations (Scopus)


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 (19)F 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.

Original languageEnglish
Pages (from-to)956-963
Number of pages8
JournalChemical Science
Issue number2
Publication statusPublished - 19 Feb 2015

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    Brem, J., Struwe, W. B., Rydzik, A. M., Tarhonskaya, H., Pfeffer, I., Flashman, E., van Berkel, S. S., Spencer, J., Claridge, T. D. W., McDonough, M. A., Benesch, J. L. P., & Schofield, C. J. (2015). Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1. Chemical Science, 6(2), 956-963.