5wih

Structure of New Delhi Metallo-Beta-lactamase 12 (NDM-12)

spinqualitylabelsall models 5wih, resolution 1.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5wih is a 1 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 1.35Å Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A024FRL9_ECOLX Publication Abstract from PubMed Use and misuse of antibiotics have driven the evolution of serine beta-lactamases to better recognize new generations of beta-lactam drugs, but the selective pressures driving evolution of metallo-beta-lactamases are less clear. Here, we present evidence that New Delhi metallo-beta-lactamase (NDM) is evolving to overcome the selective pressure of zinc(II) scarcity. Studies of NDM-1, NDM-4 (M154L), and NDM-12 (M154L, G222D) demonstrate that the point mutant M154L, contained in 50% of clinical NDM variants, selectively enhances resistance to the penam ampicillin at low zinc(II) concentrations relevant to infection sites. Each of the clinical variants is shown to be progressively more thermostable and to bind zinc(II) more tightly than NDM-1, but a selective enhancement of penam turnover at low zinc(II) concentrations indicates that most of the improvement derives from catalysis rather than stability. X-ray crystallography of NDM-4 and NDM-12, as well as bioinorganic spectroscopy of dizinc(II), zinc(II)/cobalt(II), and dicobalt(II) metalloforms probe the mechanism of enhanced resistance and reveal perturbations of the dinuclear metal cluster that underlie improved catalysis. These studies support the proposal that zinc(II) scarcity, rather than changes in antibiotic structure, is driving the evolution of new NDM variants in clinical settings. Clinical Variants of New Delhi Metallo-beta-Lactamase Are Evolving To Overcome Zinc Scarcity.,Stewart AC, Bethel CR, VanPelt J, Bergstrom A, Cheng Z, Miller CG, Williams C, Poth R, Morris M, Lahey O, Nix JC, Tierney DL, Page RC, Crowder MW, Bonomo RA, Fast W ACS Infect Dis. 2017 Dec 8;3(12):927-940. doi: 10.1021/acsinfecdis.7b00128. Epub , 2017 Oct 11. PMID:28965402 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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