Gene Rv3710
in Mycobacterium tuberculosis H37Rv
General annotation
| Type | CDS |
| Function | Involved in leucine biosynthesis (at the first step). Catalyzes condensation of acetyl-CoA and 2-oxoisovalerate to form 2-isopropylmalate synthase [catalytic activity: 3-carboxy-3-hydroxy-4-methylpentanoate + CoA = acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O]. |
| Product | 2-isopropylmalate synthase LeuA (alpha-isopropylmalate synthase) (alpha-IPM synthetase) (IPMS) |
| Comments | Rv3710, (MTV025.058), len: 644 aa. LeuA, alpha-isopropylmalate synthase (see citations below), equivalent to Q9CB76|LEUA|ML2324 2-isopropylmalate synthase from Mycobacterium leprae (607 aa), FASTA scores: opt: 3291, E(): 3.7e-192, (80.7% identity in 642 aa overlap). Also highly similar to many e.g. P42455|LEU1_CORGL|LEUA from Corynebacterium glutamicum (Brevibacterium flavum) (616 aa), FASTA scores: opt: 2547, E(): 5.3e-147, (63.25% identity in 645 aa overlap); O31046|LEU1_STRCO|LEUA from Streptomyces coelicolor (573 aa), FASTA scores: opt: 2226, E(): 1.5e-127, (57.8% identity in 616 aa overlap); BAB49833|Q98HN3|MLR2792 from Rhizobium loti (Mesorhizobium loti) (588 aa), FASTA scores: opt: 1849, E(): 1.1e-104, (58.0% identity in 536 aa overlap); etc. Equivalent to AAK48181 from Mycobacterium tuberculosis strain CDC1551 (659 aa) but shorter 15 aa. Contains PS00815 and PS00816 Alpha-isopropylmalate and homocitrate synthases signatures 1 and 2. Belongs to the alpha-IPM synthetase / homocitrate synthase family. K+ is likely the physiological activator; Zn2+ and Cd2+ are inhibitors. |
| Functional category | Intermediary metabolism and respiration |
| Proteomics | The product of this CDS corresponds to spot 1_186 identified by proteomics at the Max Planck Institute for Infection Biology, Berlin (Germany) and the Statens Serum Institute (Denmark) (see proteomics citations). Identified in culture filtrates of M. tuberculosis H37Rv (See Malen et al., 2007). Identified in the cell membrane fraction of M. tuberculosis H37Rv using 2DLC/MS (See Mawuenyega 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 90 days but not 30 days (See Kruh et al., 2010). Identified by mass spectrometry in the culture filtrate, membrane protein fraction, and whole cell lysates of M. tuberculosis H37Rv (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). Essential gene for in vitro growth of H37Rv, by analysis of saturated Himar1 transposon libraries (see DeJesus et al. 2017). 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 | 4153740 | 4155674 | + |
Genomic sequence
Feature type
Upstream flanking region (bp)
Downstream flanking region (bp)
Update
Protein sequence
>Mycobacterium tuberculosis H37Rv|Rv3710|leuA
VTTSESPDAYTESFGAHTIVKPAGPPRVGQPSWNPQRASSMPVNRYRPFAEEVEPIRLRNRTWPDRVIDRAPLWCAVDLRDGNQALIDPMSPARKRRMFDLLVRMGYKEIEVGFPSASQTDFDFVREIIEQGAIPDDVTIQVLTQCRPELIERTFQACSGAPRAIVHFYNSTSILQRRVVFRANRAEVQAIATDGARKCVEQAAKYPGTQWRFEYSPESYTGTELEYAKQVCDAVGEVIAPTPERPIIFNLPATVEMTTPNVYADSIEWMSRNLANRESVILSLHPHNDRGTAVAAAELGFAAGADRIEGCLFGNGERTGNVCLVTLGLNLFSRGVDPQIDFSNIDEIRRTVEYCNQLPVHERHPYGGDLVYTAFSGSHQDAINKGLDAMKLDADAADCDVDDMLWQVPYLPIDPRDVGRTYEAVIRVNSQSGKGGVAYIMKTDHGLSLPRRLQIEFSQVIQKIAEGTAGEGGEVSPKEMWDAFAEEYLAPVRPLERIRQHVDAADDDGGTTSITATVKINGVETEISGSGNGPLAAFVHALADVGFDVAVLDYYEHAMSAGDDAQAAAYVEASVTIASPAQPGEAGRHASDPVTIASPAQPGEAGRHASDPVTSKTVWGVGIAPSITTASLRAVVSAVNRAAR
Bibliography
- Namwat W et al. [1998]. The genetic diversity of Mycobacterium tuberculosis strains in Thailand studied by amplification of DNA segments containing direct repetitive sequences. Sequence Secondary
- Jungblut PR, Schaible UE, Mollenkopf HJ, Zimny-Arndt U, Raupach B, Mattow J, Halada P, Lamer S, Hagens K and Kaufmann SH [1999]. Comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis BCG strains: towards functional genomics of microbial pathogens. Proteomics
- Rosenkrands I et al. [2000]. Towards the proteome of Mycobacterium tuberculosis. Proteomics
- Sassetti CM et al. [2003]. Genes required for mycobacterial growth defined by high density mutagenesis. Mutant
- Koon N et al. [2004]. Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in leucine biosynthesis. Structure
- Mawuenyega KG et al. [2005]. Mycobacterium tuberculosis functional network analysis by global subcellular protein profiling. Proteomics
- de Carvalho LP et al. [2006]. Kinetic analysis of the effects of monovalent cations and divalent metals on the activity of Mycobacterium tuberculosis alpha-isopropylmalate synthase. Biochemistry
- de Carvalho LP et al. [2006]. Kinetic and chemical mechanism of alpha-isopropylmalate synthase from Mycobacterium tuberculosis. Biochemistry
- Målen H et al. [2007]. Comprehensive analysis of exported proteins from Mycobacterium tuberculosis H37Rv. Proteomics
- Singh K et al. [2007]. Cation induced differential effect on structural and functional properties of Mycobacterium tuberculosis alpha-isopropylmalate synthase. Biochemistry
- de Carvalho LP et al. [2009]. Kinetic evidence for interdomain communication in the allosteric regulation of alpha-isopropylmalate synthase from Mycobacterium tuberculosis. Biochemistry Mutant
- 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
