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

DOI: 10.1039/C4SC01752H DOI Help
PMID: 25717359 PMID Help

Authors: Jurgen Brem (University of Oxford) , Weston B. Struwe (University of Oxford) , Anna M. Rydzik (University of Oxford) , Hanna Tarhonskaya (University of Oxford) , Inga Pfeffer (University of Oxford) , Emily Flashman (University of Oxford) , Sander S. Van Berkel (University of Oxford) , James Spencer (University of Bristol) , Timothy D. W. Claridge (University of Oxford) , Michael A. Mcdonough (University of Oxford) , Justin L. P. Benesch (University of Oxford) , Christopher J. Schofield (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Chemical Science , VOL 6 (2) , PAGES 956 - 963

State: Published (Approved)
Published: October 2014

Open Access Open Access

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.

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography