TB Genome Annotation Portal

Rv2497c (bkdA)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: pyruvate dehydrogenase (acetyl-transferring) E1 component alpha subunit
  • REFSEQ: pyruvate dehydrogenase E1 component alpha subunit PdhA
  • PATRIC: Branched-chain alpha-keto acid dehydrogenase E1 component alpha subunit (EC 1.2.4.4)
  • TUBERCULIST: Probable branched-chain keto acid dehydrogenase E1 component alpha subunit BkdA
  • NCBI: Probable branched-chain keto acid dehydrogenase E1 component, alpha subunit BkdA
  • updated information (H37Rv4):
    • gene name: bkdA
    • function:
    • reference:
• Coordinates in H37Rv: 2810993 - 2812096
• Gene length: 1104 bp (with stop codon), 367 aa (without stop codon)
• Operon:


• Trans-membrane region:
  
• Role: I.B.2 - Pyruvate dehydrogenase
• GO terms:
  • GO:0055114 - oxidation-reduction process (Uniprot)
  • GO:0046872 - metal ion binding (Uniprot)
  • GO:0016624 - oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor (Uniprot)
  • GO:0016491 - oxidoreductase activity (Uniprot)
  • GO:0008152 - metabolic process (Uniprot)
  • GO:0005515 - protein binding (Uniprot)
  • GO:0003863 - 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • LIPO[c] + OXOMETHYLPENTANOATE[c] -> CO2[c] + 2MBUTLIPO[c]
  • LIPO[c] + MOP[c] -> CO2[c] + 3MBUTLIPO[c]
  • LIPO[c] + OMVAL[c] -> CO2[c] + IBUTLIPO[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:
• Search for Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  1UMD	40%	Thermus thermophilus	branched-chain 2-oxo acid dehydrogenase (E1) from Thermus thermophilus HB8 with 4-methyl-2-oxopentanoate as an intermediate
  1UMC	40%	Thermus thermophilus	branched-chain 2-oxo acid dehydrogenase (E1) from Thermus thermophilus HB8 with 4-methylpentanoate
  1UMB	40%	Thermus thermophilus	branched-chain 2-oxo acid dehydrogenase (E1) from Thermus thermophilus HB8 in holo-form
  1UM9	40%	Thermus thermophilus	branched-chain 2-oxo acid dehydrogenase (E1) from Thermus thermophilus HB8 in apo-form
  3DV0	39%	Bacillus stearothermophilus	Snapshots of catalysis in the E1 subunit of the pyruvate dehydrogenase multi-enzyme complex
  3DUF	39%	Bacillus stearothermophilus	Snapshots of catalysis in the E1 subunit of the pyruvate dehydrogenase multi-enzyme complex
  1W85	39%	GEOBACILLUS STEAROTHERMOPHILUS	The crystal structure of pyruvate dehydrogenase E1 bound to the peripheral subunit binding domain of E2
  2BFF	38%	HOMO SAPIENS	Reactivity modulation of human branched-chain alpha-ketoacid dehydrogenase by an internal molecular switch
  2BEW	38%	HOMO SAPIENS	Reactivity modulation of human branched-chain alpha-ketoacid dehydrogenase by an internal molecular switch
  2BEV	38%	HOMO SAPIENS	Reactivity modulation of human branched-chain alpha-ketoacid dehydrogenase by an internal molecular switch

• Links to additional information on bkdA:
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = 0.956 (from Jeremy Rock's lab)
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology

Amino Acid Sequence

MGEGSRRPSGMLMSVDLEPVQLVGPDGTPTAERRYHRDLPEETLRWLYEMMVVTRELDTEFVNLQRQGELALYTPCRGQEAAQVGAAACLRKTDWLFPQY
RELGVYLVRGIPPGHVGVAWRGTWHGGLQFTTKCCAPMSVPIGTQTLHAVGAAMAAQRLDEDSVTVAFLGDGATSEGDVHEALNFAAVFTTPCVFYVQNN
QWAISMPVSRQTAAPSIAHKAIGYGMPGIRVDGNDVLACYAVMAEAAARARAGDGPTLIEAVTYRLGPHTTADDPTRYRSQEEVDRWATLDPIPRYRTYL
QDQGLWSQRLEEQVTARAKHVRSELRDAVFDAPDFDVDEVFTTVYAEITPGLQAQREQLRAELARTD

Additional Information

Analysis of Positive Selection in Clinical Isolates *new*

• data from Culviner et al (2025) (55,259 Mtb clinical isolates)
  • overall pN/pS for Rv2497c: 0.650574495
  • lineage-specific pN/pS in L1: 0.478051777
  • lineage-specific pN/pS in L2: 1.027064365
  • lineage-specific pN/pS in L3: 0.462401273
  • lineage-specific pN/pS in L4: 0.686717523

• 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)	2.42 (0.69)	2.09 (0.54)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link