EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural mechanism for statin inhibition of HMG-CoA reductase.
ジャーナル・号・ページ	Science, Vol. 292, Page 1160-1164, Year 2001
掲載日	2001年1月9日 (構造データの登録日)
著者	E S Istvan / J Deisenhofer /
PubMed 要旨	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 ...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.
リンク	Science / PubMed:11349148
手法	X線回折
解像度	2.1 - 2.33 Å
構造データ	PDB-1hw8: COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH COMPACTIN (ALSO KNOWN AS MEVASTATIN) 手法: X-RAY DIFFRACTION / 解像度: 2.1 Å PDB-1hw9: COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH SIMVASTATIN 手法: X-RAY DIFFRACTION / 解像度: 2.33 Å PDB-1hwi: COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH FLUVASTATIN 手法: X-RAY DIFFRACTION / 解像度: 2.3 Å PDB-1hwj: COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH CERIVASTATIN 手法: X-RAY DIFFRACTION / 解像度: 2.26 Å PDB-1hwk: COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH ATORVASTATIN 手法: X-RAY DIFFRACTION / 解像度: 2.22 Å PDB-1hwl: COMPLEX OF THE CATALYTIC PORTION OF HUMAN HMG-COA REDUCTASE WITH ROSUVASTATIN (FORMALLY KNOWN AS ZD4522) 手法: X-RAY DIFFRACTION / 解像度: 2.1 Å
化合物	ChemComp-114: (3R,5R)-3,5-dihydroxy-7-[(1S,2S,8S,8aR)-2-methyl-8-{[(2S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]h / コンパクチン酸 ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM ChemComp-HOH: WATER ChemComp-SIM: Simvastatin acid / シンバスタチン酸 / 薬剤YM ChemComp-115: (3R,5S,6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid ChemComp-116: 7-[4-(4-FLUORO-PHENYL)-5-HYDROXYMETHYL-2,6-DIISOPROPYL-PYRIDIN-3-YL]-3,5-DIHYDROXY-HEPTANOIC ACID ChemComp-117: 7-[2-(4-FLUORO-PHENYL)-5-ISOPROPYL-3-PHENYL-4-PHENYLCARBAMOYL-PYRROL-1-YL]- 3,5-DIHYDROXY-HEPTANOIC ACID / アトルバスタチン / 薬剤YM ChemComp-FBI: 7-[4-(4-FLUORO-PHENYL)-6-ISOPROPYL-2-(METHANESULFONYL-METHYL-AMINO)-PYRIMIDIN-5-YL] -3,5-DIHYDROXY-HEPTANOIC ACID / 薬剤YM
由来	homo sapiens (ヒト)
キーワード	OXIDOREDUCTASE / protein-inhibitor complex