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

doi:10.1126/science.279.5347.98

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

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

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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 language	English (US)
Pages (from-to)	98-102
Number of pages	5
Journal	Science
Volume	279
Issue number	5347
DOIs	https://doi.org/10.1126/science.279.5347.98
State	Published - Jan 2 1998
Externally published	Yes

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10.1126/science.279.5347.98

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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.",

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AU - Jacobs, William R.

AU - Sacchettini, James C.

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AB - 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.

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

Abstract

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