Gene Rv0533c (mtFabH)
in Mycobacterium tuberculosis H37Rv
General annotation
| Type | CDS |
| Function | Involved in fatty acid biosynthesis. Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. KAS III catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities [catalytic activity: acyl-[acyl-carrier protein] + malonyl-[acyl-carrier protein] = 3-oxoacyl-[acyl-carrier protein] + CO2 + [acyl-carrier protein]]. |
| Product | 3-oxoacyl-[acyl-carrier-protein] synthase III FabH (beta-ketoacyl-ACP synthase III) (KAS III) |
| Comments | Rv0533c, (MTCY25D10.12c), len: 335 aa. FabH (alternate gene name: mtFabH), 3-oxoacyl-[acyl-carrier protein] synthase III (see citations below), highly similar to others e.g. Q54206|FABH from streptomyces glaucescens (333 aa), FASTA scores: opt: 1109, E(): 0, (51.4% identity in 333 aa overlap); FABH_ECOLI|P24249 3-oxoacyl-[acyl-carrier-protein] synthase III (317 aa), FASTA scores: opt: 666, E(): 0, (37.1% identity in 318 aa overlap); etc. Belongs to the FabH family. |
| Functional category | Lipid metabolism |
| Proteomics | 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 90 days but not 30 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). Translational start site supported by proteomics data (See Kelkar et al., 2011). |
| Mutant | Non-essential gene for in vitro growth of H37Rv in a MtbYM rich medium, by Himar1 transposon mutagenesis (see Minato et al. 2019). Non-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 and CDC1551 strains (see Sassetti et al., 2003 and Lamichhane et al., 2003). Non-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 | 624473 | 625480 | - |
Genomic sequence
Feature type
Upstream flanking region (bp)
Downstream flanking region (bp)
Update
Protein sequence
>Mycobacterium tuberculosis H37Rv|Rv0533c|fabH
MTEIATTSGARSVGLLSVGAYRPERVVTNDEICQHIDSSDEWIYTRTGIKTRRFAADDESAASMATEACRRALSNAGLSAADIDGVIVTTNTHFLQTPPAAPMVAASLGAKGILGFDLSAGCAGFGYALGAAADMIRGGGAATMLVVGTEKLSPTIDMYDRGNCFIFADGAAAVVVGETPFQGIGPTVAGSDGEQADAIRQDIDWITFAQNPSGPRPFVRLEGPAVFRWAAFKMGDVGRRAMDAAGVRPDQIDVFVPHQANSRINELLVKNLQLRPDAVVANDIEHTGNTSAASIPLAMAELLTTGAAKPGDLALLIGYGAGLSYAAQVVRMPKG
Bibliography
- Choi KH, Kremer L, Besra GS and Rock CO [2000]. Identification and substrate specificity of beta -ketoacyl (acyl carrier protein) synthase III (mtFabH) from Mycobacterium tuberculosis. Product Function
- Kremer L, Nampoothiri KM, Lesjean S, Dover LG, Graham S, Betts J, Brennan PJ, Minnikin DE, Locht C and Besra GS [2001]. Biochemical characterization of acyl carrier protein (AcpM) and malonyl-CoA:AcpM transacylase (mtFabD), two major components of Mycobacterium tuberculosis fatty acid synthase II. Secondary Function
- Scarsdale JN et al. [2001]. Crystal structure of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III. Structure
- Sassetti CM et al. [2003]. Genes required for mycobacterial growth defined by high density mutagenesis. Mutant
- Lamichhane G et al. [2003]. A postgenomic method for predicting essential genes at subsaturation levels of mutagenesis: application to Mycobacterium tuberculosis. Mutant
- Brown AK, Sridharan S, Kremer L, Lindenberg S, Dover LG, Sacchettini JC and Besra GS [2005]. Probing the mechanism of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III mtFabH: factors influencing catalysis and substrate specificity. Structure
- Musayev F, Sachdeva S, Scarsdale JN, Reynolds KA and Wright HT [2005]. Crystal structure of a substrate complex of Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III (FabH) with lauroyl-coenzyme A. Structure
- Bhatt A, Molle V, Besra GS, Jacobs WR and Kremer L [2007]. The Mycobacterium tuberculosis FAS-II condensing enzymes: their role in mycolic acid biosynthesis, acid-fastness, pathogenesis and in future drug development. Review
- Sachdeva S et al. [2008]. Separate entrance and exit portals for ligand traffic in Mycobacterium tuberculosis FabH. Structure
- Sachdeva S et al. [2008]. Probing reactivity and substrate specificity of both subunits of the dimeric Mycobacterium tuberculosis FabH using alkyl-CoA disulfide inhibitors and acyl-CoA substrates. Structure
- Al-Balas Q et al. [2009]. Identification of 2-aminothiazole-4-carboxylate derivatives active against Mycobacterium tuberculosis H37Rv and the beta-ketoacyl-ACP synthase mtFabH. Chemistry
- 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
- Kelkar DS et al. [2011]. Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry. Proteomics Sequence
- 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
