TB Genome Annotation Portal

Rv2495c (bkdC)

• Current annotations:
  • TBCAP: (community-based annotations - see table at bottom of page)
  • TBDB: pyruvate dehydrogenase E2 component (dihydrolipoamide acetyltransferase)
  • REFSEQ: branched-chain alpha-keto acid dehydrogenase subunit E2
  • PATRIC: Dihydrolipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex (EC 2.3.1.168)
  • TUBERCULIST: Probable branched-chain keto acid dehydrogenase E2 component BkdC
  • NCBI: Probable branched-chain keto acid dehydrogenase E2 component BkdC
  • updated information (H37Rv4):
    • gene name: bkdC
    • function:
    • reference:
• Type: Not Target
• Start: 2808758
• End: 2809939
• Operon:


• Trans-membrane region:
  
• Role: I.B.2 - Pyruvate dehydrogenase
• GO terms:
  • GO:0043754 - dihydrolipoyllysine-residue (2-methylpropanoyl)transferase activity (Uniprot)
  • GO:0016746 - transferase activity, transferring acyl groups (Uniprot)
  • GO:0016740 - transferase activity (Uniprot)
  • GO:0008152 - metabolic process (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0005618 - cell wall (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • COA[c] + 2MBUTLIPO[c] <=> DLIPO[c] + 2MBUTCOA[c]
  • COA[c] + 3MBUTLIPO[c] <=> DLIPO[c] + 3MBUTCOA[c]
  • COA[c] + IBUTLIPO[c] <=> DLIPO[c] + IBUTCOA[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: 3l60
• Search for Homologs in PDB
• Top 10 Homologs in PDB (as of Nov 2020):
  

  PDB	aa ident	species	PDB title
  3L60	100%	Mycobacterium tuberculosis	Crystal structure of branched-chain alpha-keto acid dehydrogenase subunit e2 from mycobacterium tuberculosis
  2L5T	47%	Thermoplasma acidophilum	Solution NMR structure of E2 lipoyl domain from Thermoplasma acidophilum
  6L1Q	43%	Acidithiobacillus ferrooxidans ATCC 23270	Crystal structure of AfCbbQ2, a MoxR AAA+-ATPase and CbbQO-type Rubisco activase from Acidithiobacillus ferrooxidans
  1LAC	43%	Geobacillus stearothermophilus	THREE-DIMENSIONAL STRUCTURE OF THE LIPOYL DOMAIN FROM BACILLUS STEAROTHERMOPHILUS PYRUVATE DEHYDROGENASE MULTIENZYME COMPLEX
  1LAB	43%	Geobacillus stearothermophilus	THREE-DIMENSIONAL STRUCTURE OF THE LIPOYL DOMAIN FROM BACILLUS STEAROTHERMOPHILUS PYRUVATE DEHYDROGENASE MULTIENZYME COMPLEX
  1K8O	41%	Homo sapiens	Solution Structure of the Lipoic Acid-Bearing Domain of the E2 component of Human, Mitochondrial Branched-Chain alpha-Ketoacid Dehydrogenase
  1K8M	41%	Homo sapiens	Solution Structure of the Lipoic Acid-Bearing Domain of the E2 component of Human, Mitochondrial Branched-Chain alpha-Ketoacid Dehydrogenase
  1QJO	41%	ESCHERICHIA COLI BL21(DE3)	INNERMOST LIPOYL DOMAIN OF THE PYRUVATE DEHYDROGENASE FROM ESCHERICHIA COLI
  2K7V	36%	Escherichia coli	Deletions in a surface loop divert the folding of a protein domain into a metastable dimeric form
  1IYV	35%	Azotobacter vinelandii	LIPOYL DOMAIN OF PYRUVATE DEHYDROGENASE COMPLEX, NMR, 29 STRUCTURES

• Links to additional information on bkdC:
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = 0.65 (from Jeremy Rock's lab)

Amino Acid Sequence

MSGEDSIRSFPVPDLGEGLQEVTVTCWSVAVGDDVEINQTLCSVETAKAEVEIPSPYAGRIVELGGAEGDVLKVGAELVRIDTGPTAVAQPNGEGAVPTL
VGYGADTAIETSRRTSRPLAAPVVRKLAKELAVDLAALQRGSGAGGVITRADVLAAARGGVGAGPDVRPVHGVHARMAEKMTLSHKEIPTAKASVEVICA
ELLRLRDRFVSAAPEITPFALTLRLLVIALKHNVILNSTWVDSGEGPQVHVHRGVHLGFGAATERGLLVPVVTDAQDKNTRELASRVAELITGAREGTLT
PAELRGSTFTVSNFGALGVDDGVPVINHPEAAILGLGAIKPRPVVVGGEVVARPTMTLTCVFDHRVVDGAQVAQFMCELRDLIESPETALLDL

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)	2.08 (0.51)	1.45 (0.54)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link