5ypk

Crystal structure of NDM-1 bound to hydrolyzed imipenem representing an EI2 complex

spinqualitylabelsall models 5ypk, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ypk is a 8 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: CL, HIW, NA, SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function E5KIY2_ECOLX Publication Abstract from PubMed New Delhi metallo-beta-lactamases (NDMs), the recent additions to metallo-beta-lactamases (MBLs), pose a serious public health threat due to its highly efficient hydrolysis of beta-lactam antibiotics and rapid worldwide dissemination. The MBL-hydrolyzing mechanism for carbapenems is less studied than that of penicillins and cephalosporins. Here, we report crystal structures of NDM-1 in complex with hydrolyzed imipenem and meropenem, at resolutions of 1.80-2.32 A, together with NMR spectra monitoring meropenem hydrolysis. Three enzyme-intermediate/product derivatives, EI1, EI2, and EP, are trapped in these crystals. Our structural data reveal double-bond tautomerization from Delta(2) to Delta(1), absence of a bridging water molecule and an exclusive beta-diastereomeric product, all suggesting that the hydrolytic intermediates are protonated by a bulky water molecule incoming from the beta-face. These results strongly suggest a distinct mechanism of NDM-1-catalyzed carbapenem hydrolysis from that of penicillin or cephalosporin hydrolysis, which may provide a novel rationale for design of mechanism-based inhibitors. The mechanism of NDM-1-catalyzed carbapenem hydrolysis is distinct from that of penicillin or cephalosporin hydrolysis.,Feng H, Liu X, Wang S, Fleming J, Wang DC, Liu W Nat Commun. 2017 Dec 21;8(1):2242. doi: 10.1038/s41467-017-02339-w. PMID:29269938 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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