1TVE

Homoserine Dehydrogenase in complex with 4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol

1TVE の概要

• エントリーDOI: 10.2210/pdb1tve/pdb
• 関連するPDBエントリー: 1EBF 1EBU 1Q7G
• 分子名称: Homoserine dehydrogenase, 4-(4-HYDROXY-3-ISOPROPYLPHENYLTHIO)-2-ISOPROPYLPHENOL (2 entities in total)
• 機能のキーワード: antifungal; small molecule screening; amino acid biosynthesis, oxidoreductase
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77432.39

構造登録者

Ejim, L.,Mirza, I.A.,Capone, C.,Nazi, I.,Jenkins, S.,Chee, G.L.,Berghuis, A.M.,Wright, G.D. (登録日: 2004-06-29, 公開日: 2004-07-13, 最終更新日: 2023-08-23)

主引用文献

Ejim, L.,Mirza, I.A.,Capone, C.,Nazi, I.,Jenkins, S.,Chee, G.L.,Berghuis, A.M.,Wright, G.D.
New phenolic inhibitors of yeast homoserine dehydrogenase
Bioorg.Med.Chem., 12:3825-3830, 2004

PubMed Abstract: 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.

PubMed: 15210149
DOI: 10.1016/j.bmc.2004.05.009

実験手法

X-RAY DIFFRACTION (3 Å)