TB Genome Annotation Portal

Rv0462 (lpdC)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: dihydrolipoyl dehydrogenase
  • REFSEQ: dihydrolipoamide dehydrogenase
  • PATRIC: Dihydrolipoamide dehydrogenase (EC 1.8.1.4)
  • TUBERCULIST: Dihydrolipoamide dehydrogenase LpdC (lipoamide reductase (NADH)) (lipoyl dehydrogenase) (dihydrolipoyl dehydrogenase) (diaphorase)
  • NCBI: Dihydrolipoamide dehydrogenase LpdC (lipoamide reductase (NADH)) (lipoyl dehydrogenase) (dihydrolipoyl dehydrogenase) (diaphorase)
  • updated information (H37Rv4):
    • gene name: lpdC
    • function:
    • reference: Ginn (2021) PMID: 33527832
• Type: Not Target
• Start: 552614
• End: 554008
• Operon:


• Trans-membrane region:
  
• Role: I.B.2 - Pyruvate dehydrogenase
• GO terms:
  • GO:0098869 - cellular oxidant detoxification (Uniprot)
  • GO:0070404 - NADH binding (Uniprot)
  • GO:0055114 - oxidation-reduction process (Uniprot)
  • GO:0050660 - flavin adenine dinucleotide binding (Uniprot)
  • GO:0045454 - cell redox homeostasis (Uniprot)
  • GO:0045254 - pyruvate dehydrogenase complex (Uniprot)
  • GO:0040007 - growth (Uniprot)
  • GO:0035375 - zymogen binding (Uniprot)
  • GO:0022900 - electron transport chain (Uniprot)
  • GO:0016668 - oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor (Uniprot)
  • GO:0016655 - oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor (Uniprot)
  • GO:0016491 - oxidoreductase activity (Uniprot)
  • GO:0016209 - antioxidant activity (Uniprot)
  • GO:0015036 - disulfide oxidoreductase activity (Uniprot)
  • GO:0009405 - pathogenesis (Uniprot)
  • GO:0009055 - electron transfer activity (Uniprot)
  • GO:0006099 - tricarboxylic acid cycle (Uniprot)
  • GO:0006096 - glycolytic process (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0005829 - cytosol (Uniprot)
  • GO:0005737 - cytoplasm (Uniprot)
  • GO:0005576 - extracellular region (Uniprot)
  • GO:0005515 - protein binding (Uniprot)
  • GO:0004148 - dihydrolipoyl dehydrogenase activity (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • NAD[c] + DLIPO[c] <=> NADH[c] + LIPO[c]
  • MK[c] + NADPH[c] -> MKH2[c] + NADP[c]
  • NAD[c] + DHLIPOYLPROTEIN[c] <=> NADH[c] + LIPOYLPROTEIN[c]
• Gene Expression Profile (Transcriptional Responses to Drugs; Boshoff et al, 2004)
• Gene Modules extracted from cluster analysis of 249 transcriptomic datasets using ICA
• Orthologs among selected mycobacteria
• Protein structure: 3ii4, 2a8x
• Search for Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  4M52	100%	Mycobacterium tuberculosis	Structure of Mtb Lpd bound to SL827
  3II4	100%	Mycobacterium tuberculosis	Structure of mycobacterial lipoamide dehydrogenase bound to a triazaspirodimethoxybenzoyl inhibitor
  2A8X	100%	Mycobacterium tuberculosis	Crystal Structure of Lipoamide Dehydrogenase from Mycobacterium tuberculosis
  6UZI	39%	Elizabethkingia anophelis NUHP1	Crystal structure of Dihydrolipoyl dehydrogenase from Elizabethkingia anophelis NUHP1
  1EBD	39%	Geobacillus stearothermophilus	DIHYDROLIPOAMIDE DEHYDROGENASE COMPLEXED WITH THE BINDING DOMAIN OF THE DIHYDROLIPOAMIDE ACETYLASE
  2QAE	38%	Trypanosoma cruzi	Crystal Structure Analysis of Trypanosoma cruzi Lipoamide dehydrogenase
  6AWA	38%	Pseudomonas putida (strain ATCC 47054 / DSM 6125 / NCIMB 11950 / KT2440)	1.83 Angstrom Resolution Crystal Structure of Dihydrolipoyl Dehydrogenase from Pseudomonas putida in Complex with FAD and Adenosine-5'-monophosphate.
  5TR3	38%	Pseudomonas putida (strain ATCC 47054 / DSM 6125 / NCIMB 11950 / KT2440)	2.5 Angstrom Resolution Crystal Structure of Dihydrolipoyl Dehydrogenase from Pseudomonas putida in Complex with FAD.
  5U25	38%	Neisseria gonorrhoeae	Crystal structure of a dihydrolipoyl dehydrogenase from Neisseria gonorrhoeae bound to FAD
  2YQU	38%	Thermus thermophilus	Crystal structures and evolutionary relationship of two different lipoamide dehydrogenase(E3s) from Thermus thermophilus

• Links to additional information on lpdC:
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = -2.052 (from Jeremy Rock's lab)
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology

Amino Acid Sequence

VTHYDVVVLGAGPGGYVAAIRAAQLGLSTAIVEPKYWGGVCLNVGCIPSKALLRNAELVHIFTKDAKAFGISGEVTFDYGIAYDRSRKVAEGRVAGVHFL
MKKNKITEIHGYGTFADANTLLVDLNDGGTESVTFDNAIIATGSSTRLVPGTSLSANVVTYEEQILSRELPKSIIIAGAGAIGMEFGYVLKNYGVDVTIV
EFLPRALPNEDADVSKEIEKQFKKLGVTILTATKVESIADGGSQVTVTVTKDGVAQELKAEKVLQAIGFAPNVEGYGLDKAGVALTDRKAIGVDDYMRTN
VGHIYAIGDVNGLLQLAHVAEAQGVVAAETIAGAETLTLGDHRMLPRATFCQPNVASFGLTEQQARNEGYDVVVAKFPFTANAKAHGVGDPSGFVKLVAD
AKHGELLGGHLVGHDVAELLPELTLAQRWDLTASELARNVHTHPTMSEALQECFHGLVGHMINF

Additional Information

Analysis of Positive Selection in Clinical Isolates *new*

• Analysis of dN/dS (omega) in two collections of Mtb clinical isolates using GenomegaMap (Window model) (see description of methods)
  • Moldova: 2,057 clinical isolates
  • global set: 5,195 clinical isolates from 15 other countries
• In the omega plots, the black line shows the mean estimate of omega (dN/dS) at each codon, and the blue lines are the bounds for the 95% credible interval (95%CI, from MCMC sampling).
• A gene is under significant positive selection if the lower-bound of the 95%CI of omega (lower blue line) exceeds 1.0 at any codon.

	Moldova (2,057)	global set (5,195)
under significant positive selection?	NO	NO
omega peak height (95%CI lower bound)	1.73 (0.27)	1.04 (0.34)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link