1tve
From Proteopedia
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Homoserine Dehydrogenase in complex with 4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol
Overview
A relatively unexploited potential target for antimicrobial agents is the biosynthesis of essential amino acids. Homoserine dehydrogenase, which reduces aspartate semi-aldehyde to homoserine in a NAD(P)H-dependent reaction, is one such target that is required for the biosynthesis of Met, Thr, and Ile from Asp. We report a small molecule screen of yeast homoserine dehydrogenase that has identified a new class of phenolic inhibitors of this class of enzyme. X-ray crystal structural analysis of one of the inhibitors in complex with homoserine dehydrogenase reveals that these molecules bind in the amino acid binding region of the active site and that the phenolic hydroxyl group interacts specifically with the backbone amide of Gly175. These results provide the first nonamino acid inhibitors of this class of enzyme and have the potential to be exploited as leads in antifungal compound design.
About this Structure
1TVE is a Single protein structure of sequence from Saccharomyces cerevisiae with as ligand. Active as Homoserine dehydrogenase, with EC number 1.1.1.3 Full crystallographic information is available from OCA.
Reference
New phenolic inhibitors of yeast homoserine dehydrogenase., Ejim L, Mirza IA, Capone C, Nazi I, Jenkins S, Chee GL, Berghuis AM, Wright GD, Bioorg Med Chem. 2004 Jul 15;12(14):3825-30. PMID:15210149
Page seeded by OCA on Thu Feb 21 15:17:45 2008
