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

Argyrides Argyrou; Matthew W. Vetting; John S. Blanchard

doi:10.1021/ja073160k

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

Argyrides Argyrou, Matthew W. Vetting, John S. Blanchard

Biochemistry

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

Abstract

The Mycobacterium tuberculosis inhA-encoded enoyl-ACP reductase is inhibited by isonicotinoylated-NADP (INH-NADP) with a Ki 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.

Original language	English (US)
Pages (from-to)	9582-9583
Number of pages	2
Journal	Journal of the American Chemical Society
Volume	129
Issue number	31
DOIs	https://doi.org/10.1021/ja073160k
State	Published - Aug 8 2007

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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10.1021/ja073160k

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abstract = "The Mycobacterium tuberculosis inhA-encoded enoyl-ACP reductase is inhibited by isonicotinoylated-NADP (INH-NADP) with a Ki 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.",

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

Abstract

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UN SDGs

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