1a8t | pdb_00001a8t

METALLO-BETA-LACTAMASE IN COMPLEX WITH L-159,061

spinqualitylabelsall models 1a8t, resolution 2.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1a8t is a 2 chain structure with sequence from "bacteroides_inaequalis"_eggerth_and_gagnon_1933 "bacteroides inaequalis" eggerth and gagnon 1933. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 061, ZN Gene: CCRA ("Bacteroides inaequalis" Eggerth and Gagnon 1933) Activity: Beta-lactamase, with EC number 3.5.2.6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [BLAB_BACFG] Can hydrolyze carbapenem compounds. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed BACKGROUND: High level resistance to carbapenem antibiotics in gram negative bacteria such as Bacteroides fragilis is caused, in part, by expression of a wide-spectrum metallo-beta-lactamase that hydrolyzes the drug to an inactive form. Co-administration of metallo-beta-lactamase inhibitors to resistant bacteria is expected to restore the antibacterial activity of carbapenems. RESULTS: Biphenyl tetrazoles (BPTs) are a structural class of potent competitive inhibitors of metallo-beta-lactamase identified through screening and predicted using molecular modeling of the enzyme structure. The X-ray crystal structure of the enzyme bound to the BPT L-159,061 shows that the tetrazole moiety of the inhibitor interacts directly with one of the two zinc atoms in the active site, replacing a metal-bound water molecule. Inhibition of metallo-beta-lactamase by BPTs in vitro correlates well with antibiotic sensitization of resistant B. fragilis. CONCLUSIONS: BPT inhibitors can sensitize a resistant B. fragilis clinical isolate expressing metallo-beta-lactamase to the antibiotics imipenem or penicillin G but not to rifampicin. Antibiotic sensitization using biphenyl tetrazoles as potent inhibitors of Bacteroides fragilis metallo-beta-lactamase.,Toney JH, Fitzgerald PM, Grover-Sharma N, Olson SH, May WJ, Sundelof JG, Vanderwall DE, Cleary KA, Grant SK, Wu JK, Kozarich JW, Pompliano DL, Hammond GG Chem Biol. 1998 Apr;5(4):185-96. PMID:9545432 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase

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