New insight into the mechanism of action of and resistance to isoniazid:: Interaction of Mycobacterium tuberculosis enoyl-ACP reductase with INH-NADP

被引：32

作者：

Argyrou, Argyrides ^{[1
]}

Vetting, Matthew W. ^{[1
]}

Blanchard, John S. ^{[1
]}

机构：

[1] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2007年 / 129卷 / 31期

关键词：

D O I：

10.1021/ja073160k

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The Mycobacterium tuberculosis inhA-encoded enoyl-ACP reductase is inhibited by isonicotinoylated-NADP (INH-NADP) with a K-i of 130 nM. The crystal structure of the InhA:INH-NADP complex was solved. The structure revealed that it is the acyclic 4S isomer of INH-NADP that binds to the enzyme in a conformation similar to the InhA:INH-NAD complex solved previously. The in vivo implications of the mechanism of action of and resistance to isoniazid resulting from the dual ability of InhA to bind to INH-NAD and INH-NADP with high affinity are discussed.

引用

页码：9582 / +

页数：3

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