1HWI

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

1HWI の概要

• エントリーDOI: 10.2210/pdb1hwi/pdb
• 関連するPDBエントリー: 1dq8 1dq9 1dqa 1HW8 1HW9 1HWJ 1HWK 1HWL
• 分子名称: HMG-COA REDUCTASE, (3R,5S,6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: protein-inhibitor complex, oxidoreductase
• 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: 203013.56

構造登録者

Istvan, E.S.,Deisenhofer, J. (登録日: 2001-01-09, 公開日: 2001-05-11, 最終更新日: 2023-08-09)

主引用文献

Istvan, E.S.,Deisenhofer, J.
Structural mechanism for statin inhibition of HMG-CoA reductase.
Science, 292:1160-1164, 2001

PubMed Abstract: HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase (HMGR) catalyzes the committed step in cholesterol biosynthesis. Statins are HMGR inhibitors with inhibition constant values in the nanomolar range that effectively lower serum cholesterol levels and are widely prescribed in the treatment of hypercholesterolemia. We have determined structures of the catalytic portion of human HMGR complexed with six different statins. The statins occupy a portion of the binding site of HMG-CoA, thus blocking access of this substrate to the active site. Near the carboxyl terminus of HMGR, several catalytically relevant residues are disordered in the enzyme-statin complexes. If these residues were not flexible, they would sterically hinder statin binding.

PubMed: 11349148
DOI: 10.1126/science.1059344

実験手法

X-RAY DIFFRACTION (2.3 Å)