1H3A

Structures of Human Oxidosqualene Cyclase Inhibitors Bound to an Homologous Enzyme

1H3A の概要

• エントリーDOI: 10.2210/pdb1h3a/pdb
• 関連するPDBエントリー: 1GSZ 1H35 1H36 1H37 1H39 1H3B 1H3C 1SQC 2SQC 3SQC
• 分子名称: SQUALENE--HOPENE CYCLASE, (HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE, (2E)-N-ALLYL-4-{[3-(4-BROMOPHENYL)-5-FLUORO-1-METHYL-1H-INDAZOL-6-YL]OXY}-N-METHYL-2-BUTEN-1-AMINE, ... (4 entities in total)
• 機能のキーワード: isomerase, cholesterol biosynthesis, inhibitor, monotopic membrane protein
• 由来する生物種: ALICYCLOBACILLUS ACIDOCALDARIUS
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 217202.45

構造登録者

Lenhart, A.,Reinert, D.J.,Weihofen, W.A.,Aebi, J.D.,Dehmlow, H.,Morand, O.H.,Schulz, G.E. (登録日: 2002-08-24, 公開日: 2003-08-21, 最終更新日: 2024-05-08)

主引用文献

Lenhart, A.,Reinert, D.J.,Aebi, J.D.,Dehmlow, H.,Morand, O.H.,Schulz, G.E.
Binding Structures and Potencies of Oxidosqualene Cyclase Inhibitors with the Homologous Squalene-Hopene Cyclase
J.Med.Chem., 46:2083-, 2003

PubMed Abstract: The binding structures of 11 human oxidosqualene cyclase inhibitors designed as cholesterol-lowering agents were determined for the squalene-hopene cyclase from Alicyclobacillus acidocaldarius, which is the only structurally known homologue of the human enzyme. The complexes were produced by cocrystallization, and the structures were elucidated by X-ray diffraction analyses. All inhibitors were bound in the large active center cavity. The detailed binding structures are presented and discussed in the light of the IC50 values of these 11 as well as 17 other inhibitors. They provide a consistent picture for the inhibition of the bacterial enzyme and can be used to adjust and improve homology models of the human enzyme. The detailed active center structures of the two enzymes are too different to show an IC50 correlation.

PubMed: 12747780
DOI: 10.1021/JM0211218

実験手法

X-RAY DIFFRACTION (2.85 Å)