5zgp

Crystal structure of NDM-1 at pH6.2 (Bis-Tris) in complex with hydrolyzed ampicillin

spinqualitylabelsall models 5zgp, resolution 1.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5zgp is a 2 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 1.15Å Ligands: GOL, PEG, ZN, ZZ7 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 Beta-lactam antibiotics are the mainstay for the treatment of bacterial infections. However, elevated resistance to these antibiotics mediated by metallo-beta-lactamases (MBL) has become a global concern. New Delhi metallo-beta-lactamase-1 (NDM-1), a newly added member of the MBL family that can hydrolyze almost all beta-lactam antibiotics, has rapidly spread all over the world and posed serious clinical threats. Broad-spectrum and mechanism-based inhibitors against all MBLs are highly desired, but the differential mechanisms of MBLs towards different antibiotics pose a great challenge. To facilitate the design of mechanism-based inhibitors, we investigated the active-site conformational changes of NDM-1 through the determination of a series of 15 high-resolution crystal structures in native form and in complex with products, biochemical and biophysical studies, site-directed mutagenesis and molecular dynamics computation. The structural studies reveal the consistency of the active site conformations in NDM-1/products complexes and the fluctuation in native NDM-1 structures. The enzymatic measurements indicate a correlation between enzymatic activity and the active site fluctuation with more fluctuation favoring higher activity. This correlation is further validated by structural and enzymatic studies of the Q123G mutant. Our combinational studies suggest that active site conformational fluctuation promotes the enzymatic activity of NDM-1, which may guide further mechanism studies and inhibitor design. Active site conformational fluctuations promote the enzymatic activity of NDM-1.,Zhang H, Ma G, Zhu Y, Zeng L, Ahmad A, Wang C, Pang B, Fang H, Zhao L, Hao Q Antimicrob Agents Chemother. 2018 Aug 27. pii: AAC.01579-18. doi:, 10.1128/AAC.01579-18. PMID:30150473 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA