1DQ9

COMPLEX OF CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH HMG-COA

1DQ9 の概要

• エントリーDOI: 10.2210/pdb1dq9/pdb
• 分子名称: PROTEIN (HMG-COA REDUCTASE), 3-HYDROXY-3-METHYLGLUTARYL-COENZYME A (2 entities in total)
• 機能のキーワード: oxidoreductase, cholesterol biosynthesis, hmg-coa, nadph
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane; Multi-pass membrane protein: P04035
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 203712.57

構造登録者

Istvan, E.S.,Palnitkar, M.,Buchanan, S.K.,Deisenhofer, J. (登録日: 1999-12-30, 公開日: 2000-03-08, 最終更新日: 2024-02-07)

主引用文献

Istvan, E.S.,Palnitkar, M.,Buchanan, S.K.,Deisenhofer, J.
Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis.
EMBO J., 19:819-830, 2000

PubMed Abstract: 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) catalyzes the formation of mevalonate, the committed step in the biosynthesis of sterols and isoprenoids. The activity of HMGR is controlled through synthesis, degradation and phosphorylation to maintain the concentration of mevalonate-derived products. In addition to the physiological regulation of HMGR, the human enzyme has been targeted successfully by drugs in the clinical treatment of high serum cholesterol levels. Three crystal structures of the catalytic portion of human HMGR in complexes with HMG-CoA, with HMG and CoA, and with HMG, CoA and NADP(+), provide a detailed view of the enzyme active site. Catalytic portions of human HMGR form tight tetramers. The crystal structure explains the influence of the enzyme's oligomeric state on the activity and suggests a mechanism for cholesterol sensing. The active site architecture of human HMGR is different from that of bacterial HMGR; this may explain why binding of HMGR inhibitors to bacterial HMGRs has not been reported.

PubMed: 10698924
DOI: 10.1093/emboj/19.5.819

実験手法

X-RAY DIFFRACTION (2.8 Å)