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

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

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint Dive into the research topics of 'New insight into the mechanism of action of and resistance to isoniazid: Interaction of Mycobacterium tuberculosis enoyl-ACP reductase with INH-NADP'. Together they form a unique fingerprint.

  • Cite this