Gene Rv0462 (TB49.2, CIP50)
in Mycobacterium tuberculosis H37Rv
General annotation
| Type | CDS |
| Function | Involved in energy metabolism. Lipoamide dehydrogenase is the E3 component of pyruvate dehydrogenase and the alpha-ketoacid dehydrogenase complex [catalytic activity: dihydrolipoamide + NAD(+) = lipoamide + NADH]. Also involved in antioxidant defense; LPDC|Rv0462, DLAT|Rv2215, AHPD|Rv2429, and AHPC|Rv2428 constitute an NADH-dependent peroxidase and peroxynitrite reductase that provides protection against oxidative stress. |
| Product | Dihydrolipoamide dehydrogenase LpdC (lipoamide reductase (NADH)) (lipoyl dehydrogenase) (dihydrolipoyl dehydrogenase) (diaphorase) |
| Comments | Rv0462, (MTV038.06), len: 464 aa. LpdC (alternate gene name: TB49.2, CIP50), dihydrolipoamide dehydrogenase (see Argyrou & Blanchard 2001), equivalent to AAA63016.1|U15183 lipoamide dehydrogenase from Mycobacterium leprae (467 aa), FASTA scores: opt: 2583, E(): 0, (83.1% identity in 467 aa overlap). Also similar to to many e.g. P50970|DLDH_ZYMMO|X82291|ZMLPD_1 dihydrolipoamide dehydrogenase from Z.mobilis (466 aa), FASTA scores: opt: 1198, E(): 0, (42.4 % identity in 465 aa overlap); etc. Belongs to the pyridine nucleotide-disulfide oxidoreductases class-I. Binds to coronin-1 in BCG and M. tuberculosis - coronin-1 is retained on phagosomes and phagosome maturation is arrested (See Deghmane et al., 2007). LpdC|Rv0462 co-immunoprecipitates with DlaT|Rv2215 (in lpdC|Rv0462 mutant) and with BkdC|Rv2495c (in dlaT|Rv2215 mutant) (See Venugopal et al., 2011). |
| Functional category | Intermediary metabolism and respiration |
| Proteomics | The product of this CDS corresponds to spots 1_351 and 1_354 identified in culture supernatant by proteomics at the Max Planck Institute for Infection Biology, Berlin, Germany, and spots 0462 and TB49.2 identified in short term culture filtrate by proteomics at the Statens Serum Institute (Denmark) (see proteomics citations). 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 culture supernatant of M. tuberculosis H37Rv using mass spectrometry (See Mattow et al., 2003). Identified in the cytosol of M. tuberculosis H37Rv using 2DLC/MS (See Mawuenyega et al., 2005). Identified in the aqueous phase of Triton X-114 extracts of M. tuberculosis H37Rv membranes using 2-DGE and MALDI-TOF-MS (See Sinha et al., 2005). Identified in culture filtrates of M. tuberculosis H37Rv (See Malen et al., 2007). 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 days but not 90 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 de Souza et al., 2011) (See Kelkar 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). Disruption of this gene results in growth defect of H37Rv in vitro, 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). M. tuberculosis H37Rv lpdC|Rv0462 mutant does not grow with glycerol and dextrose as the sole carbon source; mutant is more sensitive to nitrite and more resistant to H2O2; mutant is cleared from the lungs of C57BL/6 and IFN-gamma -/- mice, and is not detected in the spleens of C57BL/6 mice; in C57BL/6 bone marrow-derived macrophages the mutant is killed while wild-type and complemented show some growth; in 7H9 medium, M. tuberculosis H37Rv dlaT|Rv2215 mutant survives into stationary phase while lpdC|Rv0462 mutant dies, but growth curves are similar to wild-type if dextrose and glycerol are removed; lpdC|Rv0462 and dlaT|Rv2215 mutants have elevated levels of pyruvate and derived amino acids which return to near-wild-type levels by 28 days in dlaT|Rv2215 mutant but not lpdC|Rv0462 mutant; dlaT|Rv2215 mutant shows increased growth in 7H9 with leucine or isoleucine while lpdC|Rv0462 mutant and bkdC|Rv2495c-dlaT|Rv2215 double mutant show little or no growth (See Venugopal et al., 2011). Check for mutants available at TARGET website |
Coordinates
| Type | Start | End | Orientation |
|---|---|---|---|
| CDS | 552614 | 554008 | + |
Genomic sequence
Feature type
Upstream flanking region (bp)
Downstream flanking region (bp)
Update
Protein sequence
>Mycobacterium tuberculosis H37Rv|Rv0462|lpdC
VTHYDVVVLGAGPGGYVAAIRAAQLGLSTAIVEPKYWGGVCLNVGCIPSKALLRNAELVHIFTKDAKAFGISGEVTFDYGIAYDRSRKVAEGRVAGVHFLMKKNKITEIHGYGTFADANTLLVDLNDGGTESVTFDNAIIATGSSTRLVPGTSLSANVVTYEEQILSRELPKSIIIAGAGAIGMEFGYVLKNYGVDVTIVEFLPRALPNEDADVSKEIEKQFKKLGVTILTATKVESIADGGSQVTVTVTKDGVAQELKAEKVLQAIGFAPNVEGYGLDKAGVALTDRKAIGVDDYMRTNVGHIYAIGDVNGLLQLAHVAEAQGVVAAETIAGAETLTLGDHRMLPRATFCQPNVASFGLTEQQARNEGYDVVVAKFPFTANAKAHGVGDPSGFVKLVADAKHGELLGGHLVGHDVAELLPELTLAQRWDLTASELARNVHTHPTMSEALQECFHGLVGHMINF
Bibliography
- Mollenkopf HJ et al. [1999]. A dynamic two-dimensional polyacrylamide gel electrophoresis database: the mycobacterial proteome via Internet. Proteomics
- 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
- Rosenkrands I, Weldingh K, Jacobsen S, Hansen CV, Florio W, Gianetri I and Andersen P [2000]. Mapping and identification of Mycobacterium tuberculosis proteins by two-dimensional gel electrophoresis, microsequencing and immunodetection. Proteomics
- Argyrou A and Blanchard JS [2001]. Mycobacterium tuberculosis lipoamide dehydrogenase is encoded by Rv0462 and not by the lpdA or lpdB genes. Product
- Bryk R et al. [2002]. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Function
- Mattow J, Schaible UE, Schmidt F, Hagens K, Siejak F, Brestrich G, Haeselbarth G, Muller EC, Jungblut PR and Kaufmann SH [2003]. Comparative proteome analysis of culture supernatant proteins from virulent Mycobacterium tuberculosis H37Rv and attenuated M. bovis BCG Copenhagen. Proteomics
- Sassetti CM et al. [2003]. Genes required for mycobacterial growth defined by high density mutagenesis. Mutant
- Dahl JL et al. [2003]. The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice. Regulon
- Gu S et al. [2003]. Comprehensive proteomic profiling of the membrane constituents of a Mycobacterium tuberculosis strain. Proteomics
- Rajashankar KR, Bryk R, Kniewel R, Buglino JA, Nathan CF and Lima CD [2005]. Crystal structure and functional analysis of lipoamide dehydrogenase from Mycobacterium tuberculosis. Structure
- Mawuenyega KG et al. [2005]. Mycobacterium tuberculosis functional network analysis by global subcellular protein profiling. Proteomics
- Sinha S, Kosalai K, Arora S, Namane A, Sharma P, Gaikwad AN, Brodin P and Cole ST [2005]. Immunogenic membrane-associated proteins of Mycobacterium tuberculosis revealed by proteomics. Proteomics
- Tian J, Bryk R, Shi S, Erdjument-Bromage H, Tempst P and Nathan C [2005]. Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes. Function
- Deghmane AE et al. [2007]. Lipoamide dehydrogenase mediates retention of coronin-1 on BCG vacuoles, leading to arrest in phagosome maturation. Function
- Målen H et al. [2007]. Comprehensive analysis of exported proteins from Mycobacterium tuberculosis H37Rv. Proteomics
- Målen H et al. [2010]. Definition of novel cell envelope associated proteins in Triton X-114 extracts of Mycobacterium tuberculosis H37Rv. Proteomics
- Kruh NA et al. [2010]. Portrait of a pathogen: the Mycobacterium tuberculosis proteome in vivo. Proteomics
- Venugopal A et al. [2011]. Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes. Biochemistry Mutant
- 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
- de Souza GA et al. [2011]. Proteogenomic analysis of polymorphisms and gene annotation divergences in prokaryotes using a clustered mass spectrometry-friendly database. Proteomics Sequence
- 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
