1a8t
From Proteopedia
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METALLO-BETA-LACTAMASE IN COMPLEX WITH L-159,061
Overview
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.
About this Structure
1A8T is a Single protein structure of sequence from Bacteroides fragilis with ZN and 061 as ligands. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Tue Nov 20 10:41:08 2007
