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

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.

authors

• Sacchettini, James

published proceedings

• Science

altmetric score

• 14.08

author list (cited authors)

• Rozwarski, D. A., Grant, G. A., Barton, D. H., Jacobs, W. R., & Sacchettini, J. C.

citation count

• 557

complete list of authors

• Rozwarski, DA||Grant, GA||Barton, DH||Jacobs, WR||Sacchettini, JC

publication date

• January 1998

publisher

• American Association for the Advancement of Science (AAAS)  Publisher

published in

• Science  Journal

keywords

• Antitubercular Agents
• Bacterial Proteins
• Binding Sites
• Biotransformation
• Crystallography, X-Ray
• Drug Resistance, Microbial
• Enoyl-(acyl-carrier-protein) Reductase (nadh)
• Fatty Acid Synthases
• Isoniazid
• Mass Spectrometry
• Models, Molecular
• Mutation
• Mycobacterium Tuberculosis
• Mycolic Acids
• NAD
• Oxidoreductases

PubMed Central ID

• 9417034

Digital Object Identifier (DOI)

• 10.1126/science.279.5347.98

start page

• 98

end page

• 102

volume

• 279

issue

• 5347

URL

• http://dx.doi.org/10.1126/science.279.5347.98