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

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)9582-9583
Number of pages2
JournalJournal of the American Chemical Society
Volume129
Issue number31
DOIs
StatePublished - Aug 8 2007

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Isoniazid
NADP
Mycobacterium tuberculosis
Isomers
Conformations
Oxidoreductases
Enzymes
Crystal structure
isonicotinyl-NAD

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

New insight into the mechanism of action of and resistance to isoniazid : Interaction of Mycobacterium tuberculosis enoyl-ACP reductase with INH-NADP. / Argyrou, Argyrides; Vetting, Matthew W.; Blanchard, John S.

In: Journal of the American Chemical Society, Vol. 129, No. 31, 08.08.2007, p. 9582-9583.

Research output: Contribution to journalArticle

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