4rm5

Structural and mechanistic insights into NDM-1 catalyzed hydrolysis of cephalosporins

spinqualitylabelsall models 4rm5, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4rm5 is a 4 chain structure with sequence from Klebsiella pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BLAN1_KLEPN Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin. Publication Abstract from PubMed Cephalosporins constitute a large class of beta-lactam antibiotics clinically used as antimicrobial drugs. New Dehli metallo-beta-lactamase (NDM-1) poses a global threat to human health as it confers on bacterial pathogen resistance to almost all beta-lactams, including penicillins, cephalosporins, and carbapenems. Here we report the first crystal structures of NDM-1 in complex with cefuroxime and cephalexin, as well as NMR spectra monitoring cefuroxime and cefixime hydrolysis catalyzed by NDM-1. Surprisingly, cephalosporoate intermediates were captured in both crystal structures determined at 1.3 and 2.0 A. These results provide detailed information concerning the mechanism and pathways of cephalosporin hydrolysis. We also present the crystal structure and enzyme assays of a D124N mutant, which reveals that D124 most likely plays a more structural than catalytic role. Structural and Mechanistic Insights into NDM-1 Catalyzed Hydrolysis of Cephalosporins.,Feng H, Ding J, Zhu D, Liu X, Xu X, Zhang Y, Zang S, Wang DC, Liu W J Am Chem Soc. 2014 Oct 22;136(42):14694-7. doi: 10.1021/ja508388e. Epub 2014 Oct, 7. PMID:25268575 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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