4bp0 | pdb_00004bp0
Crystal structure of the closed form of Pseudomonas aeruginosa SPM-1
Structural highlights
Publication Abstract from PubMedMetallo-beta-lactamases (MBLs) catalyse the hydrolysis of almost all beta-lactam antibiotics. We report biophysical and kinetic studies on the Sao 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 alpha3 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. Studying the active-site loop movement of the Sao Paolo metallo-beta-lactamase-1daggerElectronic supplementary information (ESI) available: Procedures for protein expression and purification, F-labelling, crystallisation, data collection, and structure determination, table of crystallographic data, table of crystallographic parameters and refinement statistics, figures showing binding mode and distances, procedures for mass spectrometry measurements, differential scanning fluorimetry measurements, stopped-flow measurements and other kinetics measurements. See DOI: 10.1039/c4sc01752hClick here for additional data file.,Brem J, Struwe WB, Rydzik AM, Tarhonskaya H, Pfeffer I, Flashman E, van Berkel SS, Spencer J, Claridge TD, McDonough MA, Benesch JL, Schofield CJ Chem Sci. 2015 Feb 19;6(2):956-963. Epub 2014 Nov 4. PMID:25717359[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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