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Showing Protein Dihydrolipoyl dehydrogenase (HMDBP14569)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP14569
Secondary Accession Numbers None
Name Dihydrolipoyl dehydrogenase
Synonyms
  1. LPD
  2. Component of peroxynitrite reductase/peroxidase complex
  3. Dihydrolipoamide dehydrogenase
  4. E3 component of alpha-ketoacid dehydrogenase complexes
  5. Component of PNR/P
Gene Name LPDC
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Lipoamide dehydrogenase is an essential component of the alpha-ketoacid dehydrogenase complexes, namely the pyruvate dehydrogenase (PDH) complex, the branched-chain alpha-ketoacid dehydrogenase (BCKADH) complex, and likely also the 2-oxoglutarate dehydrogenase (ODH) complex. Catalyzes the reoxidation of dihydrolipoyl groups which are covalently attached to the lipoate acyltransferase components (E2) of the complexes. Is also able to catalyze the transhydrogenation of NADH and thio-NAD(+) in the absence of D,L-lipoamide, and the NADH-dependent reduction of quinones in vitro.Together with AhpC, AhpD and DlaT, Lpd constitutes an NADH-dependent peroxidase active against hydrogen and alkyl peroxides as well as serving as a peroxynitrite reductase, thus protecting the bacterium against reactive nitrogen intermediates and oxidative stress generated by the host immune system.Appears to be essential for Mtb pathogenesis.
Pathways
  • Biosynthesis of cofactors
  • Biosynthesis of secondary metabolites
  • Carbon metabolism
  • Citrate cycle (TCA cycle)
  • Glycine, serine and threonine metabolism
  • Glycolysis / Gluconeogenesis
  • Glyoxylate and dicarboxylate metabolism
  • Lysine degradation
  • Microbial metabolism in diverse environments
  • Propanoate metabolism
  • Pyruvate metabolism
  • Tryptophan metabolism
  • Valine, leucine and isoleucine degradation
Reactions Not Available
GO Classification
Biological Process
cell redox homeostasis
glycolysis
tricarboxylic acid cycle
suppression by symbiont of host innate immune response
pathogenesis
Cellular Component
cytosol
plasma membrane
extracellular region
pyruvate dehydrogenase complex
Molecular Function
antioxidant activity
disulfide oxidoreductase activity
oxidoreductase activity, acting on NADH or NADPH, quinone or similar compound as acceptor
zymogen binding
flavin adenine dinucleotide binding
NADH binding
dihydrolipoyl dehydrogenase activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 464
Molecular Weight 49238.805
Theoretical pI 5.856
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P9WHH9
UniProtKB/Swiss-Prot Entry Name DLDH_MYCTU
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG: Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11;393(6685):537-44. doi: 10.1038/31159. [PubMed:9634230 ]
  2. Kelkar DS, Kumar D, Kumar P, Balakrishnan L, Muthusamy B, Yadav AK, Shrivastava P, Marimuthu A, Anand S, Sundaram H, Kingsbury R, Harsha HC, Nair B, Prasad TS, Chauhan DS, Katoch K, Katoch VM, Kumar P, Chaerkady R, Ramachandran S, Dash D, Pandey A: Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry. Mol Cell Proteomics. 2011 Dec;10(12):M111.011627. doi: 10.1074/mcp.M111.011445. Epub 2011 Oct 3. [PubMed:21969609 ]
  3. Argyrou A, Blanchard JS: Mycobacterium tuberculosis lipoamide dehydrogenase is encoded by Rv0462 and not by the lpdA or lpdB genes. Biochemistry. 2001 Sep 25;40(38):11353-63. doi: 10.1021/bi010575o. [PubMed:11560483 ]
  4. Bryk R, Lima CD, Erdjument-Bromage H, Tempst P, Nathan C: Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science. 2002 Feb 8;295(5557):1073-7. doi: 10.1126/science.1067798. Epub 2002 Jan 17. [PubMed:11799204 ]
  5. Tian J, Bryk R, Shi S, Erdjument-Bromage H, Tempst P, Nathan C: Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes. Mol Microbiol. 2005 Aug;57(3):859-68. doi: 10.1111/j.1365-2958.2005.04741.x. [PubMed:16045627 ]
  6. Venugopal A, Bryk R, Shi S, Rhee K, Rath P, Schnappinger D, Ehrt S, Nathan C: Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes. Cell Host Microbe. 2011 Jan 20;9(1):21-31. doi: 10.1016/j.chom.2010.12.004. [PubMed:21238944 ]
  7. Rajashankar KR, Bryk R, Kniewel R, Buglino JA, Nathan CF, Lima CD: Crystal structure and functional analysis of lipoamide dehydrogenase from Mycobacterium tuberculosis. J Biol Chem. 2005 Oct 7;280(40):33977-83. doi: 10.1074/jbc.M507466200. Epub 2005 Aug 10. [PubMed:16093239 ]
  8. Bryk R, Arango N, Venugopal A, Warren JD, Park YH, Patel MS, Lima CD, Nathan C: Triazaspirodimethoxybenzoyls as selective inhibitors of mycobacterial lipoamide dehydrogenase . Biochemistry. 2010 Mar 2;49(8):1616-27. doi: 10.1021/bi9016186. [PubMed:20078138 ]