2q9n | pdb_00002q9n

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

spinqualitylabelsall models 2q9n, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2q9n is a 1 chain structure with sequence from Enterobacter cloacae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: LK5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AMPC_ENTCL This protein is a serine beta-lactamase with a substrate specificity for cephalosporins. 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 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. 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):4113-21. Epub 2007 Aug 1. PMID:17665896 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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