Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis

Andréa Dessen, Annaïk Quémard, John S. Blanchard, William R. Jacobs, James C. Sacchettini

Research output: Contribution to journalArticlepeer-review

405 Scopus citations


Resistance to isoniazid in Mycobacterium tuberculosis can be mediated by substitution of alanine for serine 94 in the InhA protein, the drug's primary target. InhA was shown to catalyze the β-nicotinamide adenine dinucleotide (NADH)-specific reduction of 2-transenoyl-acyl carrier protein, an essential step in fatty acid elongation. Kinetic analyses suggested that isoniazid resistance is due to a decreased affinity of the mutant protein for NADH. The three-dimensional structures of wild-type and mutant InhA, refined to 2.2 and 2.7 angstroms, respectively, revealed that drug resistance is directly related to a perturbation in the hydrogen-bonding network that stabilizes NADH binding.

Original languageEnglish (US)
Pages (from-to)1638-1641
Number of pages4
Issue number5204
StatePublished - 1995

ASJC Scopus subject areas

  • General


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