Modification of the NADH of the Isoniazid Target (InhA) from Mycobacterium tuberculosis | Academic Article individual record
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.

author list (cited authors)
Rozwarski, D. A., Grant, G. A., Barton, D., Jacobs, W. R., & Sacchettini, J. C.
publication date
1998
published in
keywords
  • Isoniazid
  • NAD
  • Fatty Acid Synthetase Complex
  • Crystallography, X-Ray
  • Drug Resistance, Microbial
  • Enoyl-(acyl-carrier-protein) Reductase (nadh)
  • Mycolic Acids
  • Mutation
  • Mass Spectrometry
  • Biotransformation
  • Fatty Acid Synthases
  • Oxidoreductases
  • Binding Sites
  • Bacterial Proteins
  • Mycobacterium Tuberculosis
  • Antitubercular Agents
  • Models, Molecular
altmetric score

9.0

citation count

470