2q9n

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Revision as of 11:43, 21 November 2007

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spinqualitylabelsall models 2q9n, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

4-Substituted Trinems as Broad Spectrum-Lactamase Inhibitors: Structure-based Design, Synthesis and Biological Activity

Overview

A wide variety of pathogens have acquired antimicrobial resistance as an, inevitable evolutionary response to the extensive use of antibacterial, agents. In particular, one of the most widely used antibiotic structural, classes is the beta-lactams, in which the most common and the most, efficient mechanism of bacterial resistance is the synthesis of, beta-lactamases. Class C beta-lactamase enzymes are primarily, cephalosporinases, mostly chromosomally encoded, and are inducible by, exposure to some beta-lactam agents and resistant to inhibition by, marketed beta-lactamase inhibitors. In an ongoing effort to alleviate this, problem a series of novel 4-substituted trinems was designed and, synthesized. Significant in vitro inhibitory activity was measured against, the bacterial beta-lactamases of class C and additionally against class A., The lead compound LK-157 was shown to be a potent mechanism-based, inactivator. Acylation of the active site Ser 64 of the class C enzyme, beta-lactamase was observed in the solved crystal structures of two, inhibitors complexes to AmpC enzyme from E. cloacae. Structure-activity, relationships in the series reveal the importance of the trinem scaffold, for inhibitory activity and the interesting potential of the series for, further development.

About this Structure

2Q9N is a Single protein structure of sequence from Enterobacter cloacae with LK5 as ligand. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.

Reference

4-Substituted Trinems as Broad Spectrum beta-Lactamase Inhibitors: Structure-Based Design, Synthesis, and Biological Activity., Plantan I, Selic L, Mesar T, Anderluh PS, Oblak M, Prezelj A, Hesse L, Andrejasic M, Vilar M, Turk D, Kocijan A, Prevec T, Vilfan G, Kocjan D, Copar A, Urleb U, Solmajer T, J Med Chem. 2007 Aug 23;50(17):4113-4121. Epub 2007 Aug 1. PMID:17665896

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