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1i2s
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(New page: 200px<br /><applet load="1i2s" size="450" color="white" frame="true" align="right" spinBox="true" caption="1i2s, resolution 1.70Å" /> '''BETA-LACTAMASE FROM ...)
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Revision as of 14:53, 20 November 2007
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BETA-LACTAMASE FROM BACILLUS LICHENIFORMIS BS3
Overview
The Bacillus licheniformis BS3 beta-lactamase catalyzes the hydrolysis of, the beta-lactam ring of penicillins, cephalosporins, and related, compounds. The production of beta-lactamases is the most common and, thoroughly studied cause of antibiotic resistance. Although they escape, the hydrolytic activity of the prototypical Staphylococcus aureus, beta-lactamase, many cephems are good substrates for a large number of, beta-lactamases. However, the introduction of a 7alpha-methoxy, substituent, as in cefoxitin, extends their antibacterial spectrum to many, cephalosporin-resistant Gram-negative bacteria. The 7alpha-methoxy group, selectively reduces the hydrolytic action of many beta-lactamases without, having a significant effect on the affinity for the target enzymes, the, membrane penicillin-binding proteins. We report here the crystallographic, structures of the BS3 enzyme and its acyl-enzyme adduct with cefoxitin at, 1.7 A resolution. The comparison of the two structures reveals a covalent, acyl-enzyme adduct with perturbed active site geometry, involving a, different conformation of the omega-loop that bears the essential, catalytic Glu166 residue. This deformation is induced by the cefoxitin, side chain whose position is constrained by the presence of the, alpha-methoxy group. The hydrolytic water molecule is also removed from, the active site by the 7beta-carbonyl of the acyl intermediate. In light, of the interactions and steric hindrances in the active site of the, structure of the BS3-cefoxitin acyl-enzyme adduct, the crucial role of the, conserved Asn132 residue is confirmed and a better understanding of the, kinetic results emerges.
About this Structure
1I2S is a Single protein structure of sequence from Bacillus licheniformis with NA and CIT as ligands. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
Reference
Crystal structures of the Bacillus licheniformis BS3 class A beta-lactamase and of the acyl-enzyme adduct formed with cefoxitin., Fonze E, Vanhove M, Dive G, Sauvage E, Frere JM, Charlier P, Biochemistry. 2002 Feb 12;41(6):1877-85. PMID:11827533
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