Gene Rv1484
in Mycobacterium tuberculosis H37Rv
General annotation
| Type | CDS |
| Function | This isozyme is involved in mycolic acid biosynthesis. Second reductive step in fatty acid biosynthesis. Involved in the resistance against the antituberculosis drugs isoniazid and ethionamide [catalytic activity: acyl-[acyl-carrier protein] + NAD(+) = trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH]. |
| Product | NADH-dependent enoyl-[acyl-carrier-protein] reductase InhA (NADH-dependent enoyl-ACP reductase) |
| Comments | Rv1484, (MTCY277.05), len: 269 aa. InhA, NADH-dependent enoyl-[acyl-carrier-protein] reductase (see citations below). Identical to INHA_MYCTU|P46533 enoyl-[acyl-carrier-protein] reductase from Mycobacterium tuberculosis and G1155270 Mycobacterium bovis enoyl acp reductase. Some similarity to the short-chain dehydrogenases/reductases (SDR) family. |
| Functional category | Lipid metabolism |
| Proteomics | Note that in Mycobacterium bovis BCG, proteome analysis by 2D-electrophoresis and MS identified this homolog which showed increased expression inside macrophages (see citation below). Identified in the membrane fraction of M. tuberculosis H37Rv using 1D-SDS-PAGE and uLC-MS/MS (See Gu et al., 2003). Identified in the membrane fraction of M. tuberculosis H37Rv using nanoLC-MS/MS (See Xiong et al., 2005). Identified by mass spectrometry in Triton X-114 extracts of M. tuberculosis H37Rv (See Malen et al., 2010). Identified by mass spectrometry in M. tuberculosis H37Rv-infected guinea pig lungs at 30 and 90 days (See Kruh et al., 2010). Identified by mass spectrometry in the membrane protein fraction and whole cell lysates of M. tuberculosis H37Rv but not the culture filtrate (See de Souza et al., 2011). |
| Mutant | Essential gene for in vitro growth of H37Rv in a MtbYM rich medium, by Himar1 transposon mutagenesis (see Minato et al. 2019). Essential gene for in vitro growth of H37Rv, by analysis of saturated Himar1 transposon libraries (see DeJesus et al. 2017). Non essential gene by Himar1 transposon mutagenesis in H37Rv strain (see Sassetti et al., 2003). Essential gene for in vitro growth of H37Rv, by Himar1 transposon mutagenesis (See Griffin et al., 2011). Check for mutants available at TARGET website |
Coordinates
| Type | Start | End | Orientation |
|---|---|---|---|
| CDS | 1674202 | 1675011 | + |
Genomic sequence
Feature type
Upstream flanking region (bp)
Downstream flanking region (bp)
Update
Protein sequence
>Mycobacterium tuberculosis H37Rv|Rv1484|inhA
MTGLLDGKRILVSGIITDSSIAFHIARVAQEQGAQLVLTGFDRLRLIQRITDRLPAKAPLLELDVQNEEHLASLAGRVTEAIGAGNKLDGVVHSIGFMPQTGMGINPFFDAPYADVSKGIHISAYSYASMAKALLPIMNPGGSIVGMDFDPSRAMPAYNWMTVAKSALESVNRFVAREAGKYGVRSNLVAAGPIRTLAMSAIVGGALGEEAGAQIQLLEEGWDQRAPIGWNMKDATPVAKTVCALLSDWLPATTGDIIYADGGAHTQLL
Bibliography
- Banerjee A et al. [1994]. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Mutant
- Dessen A et al. [1995]. Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis. Product Structure Function
- Wilson TM et al. [1995]. Effect of inhA and katG on isoniazid resistance and virulence of Mycobacterium bovis. Homolog Mutant
- Mdluli K et al. [1996]. Biochemical and genetic data suggest that InhA is not the primary target for activated isoniazid in Mycobacterium tuberculosis. Sequence
- Rozwarski DA et al. [1998]. Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis. Structure
- Cole ST et al. [1998]. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Sequence Secondary
- Rozwarski DA et al. [1999]. Crystal structure of the Mycobacterium tuberculosis enoyl-ACP reductase, InhA, in complex with NAD+ and a C16 fatty acyl substrate. Structure
- Saint-Joanis B et al. [1999]. Use of site-directed mutagenesis to probe the structure, function and isoniazid activation of the catalase/peroxidase, KatG, from Mycobacterium tuberculosis. Secondary Mutant
- Kremer L, Baulard AR and Besra GS [2000]. Review
- Gu S et al. [2003]. Comprehensive proteomic profiling of the membrane constituents of a Mycobacterium tuberculosis strain. Proteomics
- Kuo MR et al. [2003]. Targeting tuberculosis and malaria through inhibition of Enoyl reductase: compound activity and structural data. Structure
- Sassetti CM et al. [2003]. Genes required for mycobacterial growth defined by high density mutagenesis. Mutant
- Xiong Y, Chalmers MJ, Gao FP, Cross TA and Marshall AG [2005]. Identification of Mycobacterium tuberculosis H37Rv integral membrane proteins by one-dimensional gel electrophoresis and liquid chromatography electrospray ionization tandem mass spectrometry. Proteomics
- Oliveira JS et al. [2006]. Crystallographic and pre-steady-state kinetics studies on binding of NADH to wild-type and isoniazid-resistant enoyl-ACP(CoA) reductase enzymes from Mycobacterium tuberculosis. Structure
- He X et al. [2006]. Pyrrolidine carboxamides as a novel class of inhibitors of enoyl acyl carrier protein reductase from Mycobacterium tuberculosis. Structure
- Vilchèze C et al. [2006]. Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid. Structure
- Dias MV et al. [2007]. Crystallographic studies on the binding of isonicotinyl-NAD adduct to wild-type and isoniazid resistant 2-trans-enoyl-ACP (CoA) reductase from Mycobacterium tuberculosis. Structure
- Argyrou A et al. [2007]. New insight into the mechanism of action of and resistance to isoniazid: interaction of Mycobacterium tuberculosis enoyl-ACP reductase with INH-NADP. Structure
- He X et al. [2007]. Inhibition of the Mycobacterium tuberculosis enoyl acyl carrier protein reductase InhA by arylamides. Structure
- Wang F et al. [2007]. Mechanism of thioamide drug action against tuberculosis and leprosy. Structure
- Gurvitz A et al. [2008]. 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. Function
- Kruh NA et al. [2010]. Portrait of a pathogen: the Mycobacterium tuberculosis proteome in vivo. Proteomics
- Målen H et al. [2010]. Definition of novel cell envelope associated proteins in Triton X-114 extracts of Mycobacterium tuberculosis H37Rv. Proteomics
- de Souza GA et al. [2011]. Bacterial proteins with cleaved or uncleaved signal peptides of the general secretory pathway. Proteomics
- Griffin JE et al. [2011]. High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism. Mutant
- DeJesus MA et al. [2017]. Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis. Mutant
- Minato Y et al. [2019]. Genomewide Assessment of Mycobacterium tuberculosis Conditionally Essential Metabolic Pathways. Mutant
