BKDA_MYCTU
ID BKDA_MYCTU Reviewed; 367 AA.
AC P9WIS3; F2GH61; L0T9Z4; O06161; Q7D714;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=3-methyl-2-oxobutanoate dehydrogenase subunit alpha;
DE EC=1.2.4.4;
DE AltName: Full=Branched-chain alpha-ketoacid dehydrogenase E1 component subunit alpha;
DE Short=BCKADH E1-alpha;
GN Name=bkdA; Synonyms=pdhA; OrderedLocusNames=Rv2497c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP INDUCTION BY STARVATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11929527; DOI=10.1046/j.1365-2958.2002.02779.x;
RA Betts J.C., Lukey P.T., Robb L.C., McAdam R.A., Duncan K.;
RT "Evaluation of a nutrient starvation model of Mycobacterium tuberculosis
RT persistence by gene and protein expression profiling.";
RL Mol. Microbiol. 43:717-731(2002).
RN [3]
RP NO FUNCTION AS A PDH COMPONENT, AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16045627; DOI=10.1111/j.1365-2958.2005.04741.x;
RA Tian J., Bryk R., Shi S., Erdjument-Bromage H., Tempst P., Nathan C.;
RT "Mycobacterium tuberculosis appears to lack alpha-ketoglutarate
RT dehydrogenase and encodes pyruvate dehydrogenase in widely separated
RT genes.";
RL Mol. Microbiol. 57:859-868(2005).
RN [4]
RP FUNCTION AS A BCKADH COMPONENT, INDUCTION, GENE NAME, AND IDENTIFICATION IN
RP THE BCKADH COMPLEX.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21238944; DOI=10.1016/j.chom.2010.12.004;
RA Venugopal A., Bryk R., Shi S., Rhee K., Rath P., Schnappinger D., Ehrt S.,
RA Nathan C.;
RT "Virulence of Mycobacterium tuberculosis depends on lipoamide
RT dehydrogenase, a member of three multienzyme complexes.";
RL Cell Host Microbe 9:21-31(2011).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- FUNCTION: Component of the branched-chain alpha-ketoacid dehydrogenase
CC (BCKADH) complex, that catalyzes the overall conversion of branched-
CC chain alpha-ketoacids to acyl-CoA and CO(2).
CC {ECO:0000269|PubMed:21238944}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-N(6)-lipoyl-L-lysyl-[dihydrolipoyllysine-residue (2-
CC methylpropanoyl)transferase] + 3-methyl-2-oxobutanoate + H(+) = (R)-
CC N(6)-(S(8)-2-methylpropanoyldihydrolipoyl)-L-lysyl-
CC [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] + CO2;
CC Xref=Rhea:RHEA:13457, Rhea:RHEA-COMP:10488, Rhea:RHEA-COMP:10489,
CC ChEBI:CHEBI:11851, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:83099, ChEBI:CHEBI:83142; EC=1.2.4.4;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC Evidence={ECO:0000250};
CC -!- SUBUNIT: Heteromer of E1 alpha (BkdA) and beta (BkdB) subunits. Part of
CC the BCKADH complex, consisting of multiple copies of BkdA/BkdB (E1),
CC BkdC (E2) and Lpd (E3). {ECO:0000269|PubMed:16045627,
CC ECO:0000269|PubMed:21238944}.
CC -!- INDUCTION: Up-regulated upon nutrient starvation. Is also highly up-
CC regulated in a DlaT-deficient strain. Part of the bkdABC operon.
CC {ECO:0000269|PubMed:11929527, ECO:0000269|PubMed:21238944}.
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DR EMBL; AL123456; CCP45291.1; -; Genomic_DNA.
DR PIR; A70550; A70550.
DR RefSeq; NP_217013.1; NC_000962.3.
DR RefSeq; WP_003412761.1; NZ_NVQJ01000063.1.
DR AlphaFoldDB; P9WIS3; -.
DR SMR; P9WIS3; -.
DR STRING; 83332.Rv2497c; -.
DR PaxDb; P9WIS3; -.
DR DNASU; 888583; -.
DR GeneID; 45426491; -.
DR GeneID; 888583; -.
DR KEGG; mtu:Rv2497c; -.
DR TubercuList; Rv2497c; -.
DR eggNOG; COG1071; Bacteria.
DR OMA; LQYWGGD; -.
DR PhylomeDB; P9WIS3; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0003863; F:3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity; IEA:UniProtKB-EC.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProt.
DR GO; GO:0006086; P:acetyl-CoA biosynthetic process from pyruvate; IBA:GO_Central.
DR InterPro; IPR001017; DH_E1.
DR InterPro; IPR017596; PdhA/BkdA.
DR InterPro; IPR029061; THDP-binding.
DR PANTHER; PTHR11516:SF41; PTHR11516:SF41; 1.
DR Pfam; PF00676; E1_dh; 1.
DR SUPFAM; SSF52518; SSF52518; 1.
DR TIGRFAMs; TIGR03181; PDH_E1_alph_x; 1.
PE 1: Evidence at protein level;
KW Magnesium; Metal-binding; Oxidoreductase; Reference proteome;
KW Thiamine pyrophosphate.
FT CHAIN 1..367
FT /note="3-methyl-2-oxobutanoate dehydrogenase subunit alpha"
FT /id="PRO_0000420518"
FT BINDING 99..101
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 100
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 141..142
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 170..176
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 171
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 200..204
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 200
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 269
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
SQ SEQUENCE 367 AA; 40616 MW; BB7EC516F2C55829 CRC64;
MGEGSRRPSG MLMSVDLEPV QLVGPDGTPT AERRYHRDLP EETLRWLYEM MVVTRELDTE
FVNLQRQGEL ALYTPCRGQE AAQVGAAACL RKTDWLFPQY RELGVYLVRG IPPGHVGVAW
RGTWHGGLQF TTKCCAPMSV PIGTQTLHAV GAAMAAQRLD EDSVTVAFLG DGATSEGDVH
EALNFAAVFT TPCVFYVQNN QWAISMPVSR QTAAPSIAHK AIGYGMPGIR VDGNDVLACY
AVMAEAAARA RAGDGPTLIE AVTYRLGPHT TADDPTRYRS QEEVDRWATL DPIPRYRTYL
QDQGLWSQRL EEQVTARAKH VRSELRDAVF DAPDFDVDEV FTTVYAEITP GLQAQREQLR
AELARTD
