Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis

Denise A. Rozwarski, Gregory A. Grant, Derek H.R. Barton, William R. Jacobs, James C. Sacchettini

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Abstract

The preferred antitubercular drug isoniazid specifically targets a long- chain enoyl-acyl carrier protein reductase (InhA), an enzyme essential for mycolic acid biosynthesis in Mycobacterium tuberculosis. Despite the widespread use of this drug for more than 40 years, its precise mode of action has remained obscure. Data from x-ray crystallography and mass spectrometry reveal that the mechanism of isoniazid action against InhA is covalent attachment of the activated form of the drug to the nicotinamide ring of nicotinamide adenine dinucleotide bound within the active site of InhA.

Original languageEnglish (US)
Pages (from-to)98-102
Number of pages5
JournalScience
Volume279
Issue number5347
DOIs
StatePublished - Jan 2 1998
Externally publishedYes

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Cite this

Rozwarski, D. A., Grant, G. A., Barton, D. H. R., Jacobs, W. R., & Sacchettini, J. C. (1998). Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis. Science, 279(5347), 98-102. https://doi.org/10.1126/science.279.5347.98