EC 1.3.1.118 - Meromycolic acid enoyl-[acyl-carrier-protein] reductase

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IntEnz Enzyme Nomenclature
EC 1.3.1.118

Names

Accepted name:
meromycolic acid enoyl-[acyl-carrier-protein] reductase
Other name:
inhA (gene name)
Systematic name:
meromycolyl-[acyl-carrier protein]:NAD+ oxidoreductase

Reaction

Comments:

InhA is a component of the fatty acid synthase (FAS) II system of Mycobacterium tuberculosis, catalysing an enoyl-[acyl-carrier-protein] reductase step. The enzyme acts on very long and unsaturated fatty acids that form the meromycolic component of mycolic acids. It extends FASI-derived C20 fatty acids to form C60 to C90 mycolic acids. The enzyme, which forms a homotetramer, is the target of the preferred antitubercular drug isoniazid.

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Structural data: CSA , EC2PDB

References

  1. Quemard, A., Sacchettini, J. C., Dessen, A., Vilcheze, C., Bittman, R., Jacobs, W. R., Blanchard, J. S.
    Enzymatic characterization of the target for isoniazid in Mycobacterium tuberculosis.
    Biochemistry 34 : 8235-8241 (1995). [PMID: 7599116]
  2. Rozwarski, D. A., Vilcheze, C., Sugantino, M., Bittman, R., Sacchettini, J. C.
    Crystal structure of the Mycobacterium tuberculosis enoyl-ACP reductase, InhA, in complex with NAD+ and a C16 fatty acyl substrate.
    J. Biol. Chem. 274 : 15582-15589 (1999). [PMID: 10336454]
  3. Marrakchi, H., Laneelle, G., Quemard, A.
    InhA, a target of the antituberculous drug isoniazid, is involved in a mycobacterial fatty acid elongation system, FAS-II.
    Microbiology (Reading, Engl.) 146 ( Pt 2) : 289-296 (2000). [PMID: 10708367]
  4. Vilcheze, C., Morbidoni, H. R., Weisbrod, T. R., Iwamoto, H., Kuo, M., Sacchettini, J. C., Jacobs, W. R.
    Inactivation of the inhA-encoded fatty acid synthase II (FASII) enoyl-acyl carrier protein reductase induces accumulation of the FASI end products and cell lysis of Mycobacterium smegmatis.
    J. Bacteriol. 182 : 4059-4067 (2000). [PMID: 10869086]
  5. Gurvitz, A., Hiltunen, J. K., Kastaniotis, A. J.
    Function of heterologous Mycobacterium tuberculosis InhA, a type 2 fatty acid synthase enzyme involved in extending C20 fatty acids to C60-to-C90 mycolic acids, during de novo lipoic acid synthesis in Saccharomyces cerevisiae.
    Appl. Environ. Microbiol. 74 : 5078-5085 (2008). [PMID: 18552191]
  6. Chollet, A., Mourey, L., Lherbet, C., Delbot, A., Julien, S., Baltas, M., Bernadou, J., Pratviel, G., Maveyraud, L., Bernardes-Genisson, V.
    Crystal structure of the enoyl-ACP reductase of Mycobacterium tuberculosis (InhA) in the apo-form and in complex with the active metabolite of isoniazid pre-formed by a biomimetic approach.
    J. Struct. Biol. 190 : 328-337 (2015). [PMID: 25891098]

[EC 1.3.1.118 created 2018]