6t5l

MYO-1 from Myroides odoratimimus. Environmental metallo-beta-lactamases exhibit high enzymatic activity under zinc deprivation

spinqualitylabelsall models 6t5l, resolution 2.17Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6t5l is a 2 chain structure with sequence from Ccug 39352. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, ZN Gene: AS202_20055 (CCUG 39352) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed BACKGROUND: MBLs form a large and heterogeneous group of bacterial enzymes conferring resistance to beta-lactam antibiotics, including carbapenems. A large environmental reservoir of MBLs has been identified, which can act as a source for transfer into human pathogens. Therefore, structural investigation of environmental and clinically rare MBLs can give new insights into structure-activity relationships to explore the role of catalytic and second shell residues, which are under selective pressure. OBJECTIVES: To investigate the structure and activity of the environmental subclass B1 MBLs MYO-1, SHD-1 and ECV-1. METHODS: The respective genes of these MBLs were cloned into vectors and expressed in Escherichia coli. Purified enzymes were characterized with respect to their catalytic efficiency (kcat/Km). The enzymatic activities and MICs were determined for a panel of different beta-lactams, including penicillins, cephalosporins and carbapenems. Thermostability was measured and structures were solved using X-ray crystallography (MYO-1 and ECV-1) or generated by homology modelling (SHD-1). RESULTS: Expression of the environmental MBLs in E. coli resulted in the characteristic MBL profile, not affecting aztreonam susceptibility and decreasing susceptibility to carbapenems, cephalosporins and penicillins. The purified enzymes showed variable catalytic activity in the order of <5% to approximately 70% compared with the clinically widespread NDM-1. The thermostability of ECV-1 and SHD-1 was up to 8 degrees C higher than that of MYO-1 and NDM-1. Using solved structures and molecular modelling, we identified differences in their second shell composition, possibly responsible for their relatively low hydrolytic activity. CONCLUSIONS: These results show the importance of environmental species acting as reservoirs for MBL-encoding genes. Structural and biochemical characterization of the environmental MBLs MYO-1, ECV-1 and SHD-1.,Frohlich C, Sorum V, Huber S, Samuelsen O, Berglund F, Kristiansson E, Kotsakis SD, Marathe NP, Larsson DGJ, Leiros HS J Antimicrob Chemother. 2020 May 28. pii: 5848379. doi: 10.1093/jac/dkaa175. PMID:32464640 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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