1O6H

Squalene-Hopene Cyclase

Summary for 1O6H

• Entry DOI: 10.2210/pdb1o6h/pdb
• Related: 1GSZ 1H35 1H36 1H37 1H39 1H3A 1H3B 1H3C 1O6Q 1O6R 1O79 1SQC 1UMP 2SQC 3SQC
• Descriptor: SQUALENE--HOPENE CYCLASE, (HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE, N-(6-{[1-(4-BROMOPHENYL)ISOQUINOLIN-6-YL]OXY}HEXYL)-N-METHYLPROP-2-EN-1-AMINE, ... (4 entities in total)
• Functional Keywords: isomerase, cholesterol biosynthesis, inhibitor, oxidosqualene cyclase, monotopic membrane protein
• Biological source: ALICYCLOBACILLUS ACIDOCALDARIUS
• Total number of polymer chains: 3
• Total formula weight: 217229.68

Authors

Lenhart, A.,Reinert, D.J.,Weihofen, W.A.,Aebi, J.D.,Dehmlow, H.,Morand, O.H.,Schulz, G.E. (deposition date: 2002-10-03, release date: 2003-10-02, Last modification date: 2024-05-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.8 Å)