2F9A

HMG-CoA synthase from Brassica juncea in complex with F-244

2F9A の概要

• エントリーDOI: 10.2210/pdb2f9a/pdb
• 関連するPDBエントリー: 2F82 2FA0 2FA3
• 分子名称: 3-Hydroxy-3-methylglutaryl coenzyme A synthase 1, (7R,12R,13R)-13-formyl-12,14-dihydroxy-3,5,7-trimethyltetradeca-2,4-dienoic acid (3 entities in total)
• 機能のキーワード: hmgs1, f-244, transferase
• 由来する生物種: Brassica juncea
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 50352.26

構造登録者

Pojer, F.,Ferrer, J.L.,Richard, S.B.,Noel, J.P. (登録日: 2005-12-05, 公開日: 2006-07-25, 最終更新日: 2024-10-09)

主引用文献

Pojer, F.,Ferrer, J.L.,Richard, S.B.,Nagegowda, D.A.,Chye, M.L.,Bach, T.J.,Noel, J.P.
Structural basis for the design of potent and species-specific inhibitors of 3-hydroxy-3-methylglutaryl CoA synthases.
Proc.Natl.Acad.Sci.Usa, 103:11491-11496, 2006

PubMed Abstract: 3-Hydroxy-3-methylglutaryl CoA synthase (HMGS) catalyzes the first committed step in the mevalonate metabolic pathway for isoprenoid biosynthesis and serves as an alternative target for cholesterol-lowering and antibiotic drugs. We have determined a previously undescribed crystal structure of a eukaryotic HMGS bound covalently to a potent and specific inhibitor F-244 [(E,E)-11-[3-(hydroxymethyl)-4-oxo-2-oxytanyl]-3,5,7-trimethyl-2,4-undecadienenoic acid]. Given the accessibility of synthetic analogs of the F-244 natural product, this inhibited eukaryotic HMGS structure serves as a necessary starting point for structure-based methods that may improve the potency and species-specific selectivity of the next generation of F-244 analogs designed to target particular eukaryotic and prokaryotic HMGS.

PubMed: 16864776
DOI: 10.1073/pnas.0604935103

実験手法

X-RAY DIFFRACTION (2.51 Å)