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Binding structures and potencies of oxidosqualene cyclase inhibitors with the homologous squalene-hopene cyclase.

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Lenhart A,Reinert DJ,Aebi JD,Dehmlow H,Morand OH,Schulz GE

doi

10.1021/jm0211218

keywords:

subject

Has Abstract

pub_date

2003-05-22 00:00:00

pages

2083-92

issue

11

eissn

0022-2623

issn

1520-4804

journal_volume

46

pub_type

杂志文章

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