2NV6

Mycobacterium tuberculosis InhA (S94A) bound with INH-NAD adduct

Summary for 2NV6

• Entry DOI: 10.2210/pdb2nv6/pdb
• Descriptor: Enoyl-[acyl-carrier-protein] reductase [NADH, ISONICOTINIC-ACETYL-NICOTINAMIDE-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: inha, s94a, tuberculosis, isoniazid, oxidoreductase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 1
• Total formula weight: 29146.08

Authors

Wang, F.,Sacchettini, J.C. (deposition date: 2006-11-10, release date: 2006-11-21, Last modification date: 2023-08-30)

Primary citation

Vilcheze, C.,Wang, F.,Arai, M.,Hazbon, M.H.,Colangeli, R.,Kremer, L.,Weisbrod, T.R.,Alland, D.,Sacchettini, J.C.,Jacobs Jr., W.R.
Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid.
NAT.MED. (N.Y.), 12:1027-1029, 2006

PubMed Abstract: Isoniazid is one of the most effective antituberculosis drugs, yet its precise mechanism of action is still controversial. Using specialized linkage transduction, a single point mutation allele (S94A) within the putative target gene inhA was transferred in Mycobacterium tuberculosis. The inhA(S94A) allele was sufficient to confer clinically relevant levels of resistance to isoniazid killing and inhibition of mycolic acid biosynthesis. This resistance correlated with the decreased binding of the INH-NAD inhibitor to InhA, as shown by enzymatic and X-ray crystallographic analyses, and establishes InhA as the primary target of isoniazid action in M. tuberculosis.

PubMed: 16906155
DOI: 10.1038/nm1466

Experimental method

X-RAY DIFFRACTION (1.9 Å)