ID ODBA_PSEPU Reviewed; 410 AA. AC P09060; DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 2. DT 02-SEP-2026, entry version 126. DE RecName: Full=2-oxoisovalerate dehydrogenase subunit alpha; DE EC=1.2.4.4 {ECO:0000305|PubMed:8521848}; DE AltName: Full=Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain; DE Short=BCKDH E1-alpha; GN Name=bkdA1 {ECO:0000303|PubMed:3416875}; OS Pseudomonas putida (Arthrobacter siderocapsulatus). OC Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria; OC Pseudomonadales; Pseudomonadaceae; Pseudomonas. OX NCBI_TaxID=303; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=G2; RX PubMed=3416875; DOI=10.1111/j.1432-1033.1988.tb14283.x; RA Burns G., Brown T., Hatter K., Idriss J., Sokatch J.R.; RT "Similarity of the E1 subunits of branched-chain-oxoacid dehydrogenase from RT Pseudomonas putida to the corresponding subunits of mammalian branched- RT chain-oxoacid and pyruvate dehydrogenases."; RL Eur. J. Biochem. 176:311-317(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-17. RC STRAIN=G2; RX PubMed=2211503; DOI=10.1128/jb.172.10.5655-5663.1990; RA Madhusudhan K.T., Huang G., Burns G., Sokatch J.R.; RT "Transcriptional analysis of the promoter region of the Pseudomonas putida RT branched-chain keto acid dehydrogenase operon."; RL J. Bacteriol. 172:5655-5663(1990). RN [3] RP PROTEIN SEQUENCE OF 1-13, SUBUNIT, AND MUTAGENESIS OF SER-313; SER-315 AND RP SER-319. RX PubMed=8521848; DOI=10.1111/j.1432-1033.1995.828_3.x; RA Hester K., Luo J., Burns G., Braswell E.H., Sokatch J.R.; RT "Purification of active E1 alpha 2 beta 2 of Pseudomonas putida branched- RT chain-oxoacid dehydrogenase."; RL Eur. J. Biochem. 233:828-836(1995). RN [4] {ECO:0007744|PDB:1QS0} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 2-408 IN COMPLEX WITH SUBUNIT RP BETA; MG(2+) AND THIAMINE DIPHOSPHATE, FUNCTION, COFACTOR, AND SUBUNIT. RX PubMed=10426958; DOI=10.1038/11563; RA Aevarsson A., Seger K., Turley S., Sokatch J.R., Hol W.G.J.; RT "Crystal structure of 2-oxoisovalerate and dehydrogenase and the RT architecture of 2-oxo acid dehydrogenase multienzyme complexes."; RL Nat. Struct. Biol. 6:785-792(1999). RN [5] {ECO:0007744|PDB:2BP7} RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) IN COMPLEX WITH SUBUNIT BETA, AND RP SUBUNIT. RX PubMed=16084384; DOI=10.1016/j.str.2005.04.021; RA Frank R.A., Pratap J.V., Pei X.Y., Perham R.N., Luisi B.F.; RT "The molecular origins of specificity in the assembly of a multienzyme RT complex."; RL Structure 13:1119-1130(2005). CC -!- FUNCTION: Component of the branched-chain alpha-keto dehydrogenase CC complex, which catalyzes the overall conversion of alpha-keto acids CC derived from the branched-chain amino-acids valine, leucine and CC isoleucine to acyl-CoA and CO(2) (Probable). The complex contains CC multiple copies of three enzymatic components: branched-chain alpha- CC keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and CC lipoamide dehydrogenase (E3) (Probable). The E1 subunit catalyzes the CC first step with the decarboxylation of the alpha-ketoacid forming an CC enzyme-product intermediate (Probable). {ECO:0000305|PubMed:10426958}. CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-[(R)-lipoyl]-L-lysyl-[protein] + 3-methyl-2-oxobutanoate CC + H(+) = N(6)-[(R)-S(8)-2-methylpropanoyldihydrolipoyl]-L-lysyl- CC [protein] + CO2; Xref=Rhea:RHEA:13457, Rhea:RHEA-COMP:10474, CC Rhea:RHEA-COMP:10497, ChEBI:CHEBI:11851, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16526, ChEBI:CHEBI:83099, ChEBI:CHEBI:83142; EC=1.2.4.4; CC Evidence={ECO:0000305|PubMed:8521848}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13458; CC Evidence={ECO:0000305|PubMed:8521848}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-[(R)-lipoyl]-L-lysyl-[protein] + 4-methyl-2-oxopentanoate CC + H(+) = N(6)-[(R)-S(8)-3-methylbutanoyldihydrolipoyl]-L-lysyl- CC [protein] + CO2; Xref=Rhea:RHEA:84639, Rhea:RHEA-COMP:10474, CC Rhea:RHEA-COMP:20408, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:17865, ChEBI:CHEBI:83099, ChEBI:CHEBI:233973; EC=1.2.4.4; CC Evidence={ECO:0000250|UniProtKB:P37940}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84640; CC Evidence={ECO:0000250|UniProtKB:P37940}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-[(R)-lipoyl]-L-lysyl-[protein] + (S)-3-methyl-2- CC oxopentanoate + H(+) = N(6)-{(R)-S(8)-[(2S)-2- CC methylbutanoyl]dihydrolipoyl}-L-lysyl-[protein] + CO2; CC Xref=Rhea:RHEA:84643, Rhea:RHEA-COMP:10474, Rhea:RHEA-COMP:20409, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:35146, CC ChEBI:CHEBI:83099, ChEBI:CHEBI:233974; EC=1.2.4.4; CC Evidence={ECO:0000250|UniProtKB:P37940}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84644; CC Evidence={ECO:0000250|UniProtKB:P37940}; CC -!- COFACTOR: CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937; CC Evidence={ECO:0000269|PubMed:10426958}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:10426958}; CC -!- SUBUNIT: Heterotetramer of two alpha and two beta chains. CC {ECO:0000269|PubMed:10426958, ECO:0000269|PubMed:16084384, CC ECO:0000269|PubMed:8521848}. CC -!- SIMILARITY: Belongs to the BCKDHA family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M57613; AAA65614.1; -; Genomic_DNA. DR PIR; S01317; DEPSXA. DR RefSeq; WP_019099583.1; NZ_AP022324.1. DR PDB; 1QS0; X-ray; 2.40 A; A=2-408. DR PDB; 2BP7; X-ray; 2.90 A; A/C/E/G=1-410. DR AlphaFoldDB; P09060; -. DR MDposit; P09060; -. DR SMR; P09060; -. DR DIP; DIP-6208N; -. DR IntAct; P09060; 1. DR GeneID; 83671272; -. DR eggNOG; COG1071; Bacteria. DR EvolutionaryTrace; P09060; -. DR GO; GO:0003863; F:branched-chain 2-oxo acid dehydrogenase activity; IEA:UniProtKB-EC. DR GO; GO:0009083; P:branched-chain amino acid catabolic process; IEA:TreeGrafter. DR CDD; cd02000; TPP_E1_PDC_ADC_BCADC; 1. DR Gene3D; 3.40.50.970; -; 1. DR InterPro; IPR050771; Alpha-ketoacid_DH_E1_comp. DR InterPro; IPR001017; DH_E1. DR InterPro; IPR022593; Oxoisoval_DH_suAlpha_N_dom. DR InterPro; IPR029061; THDP-binding. DR PANTHER; PTHR43380; 2-OXOISOVALERATE DEHYDROGENASE SUBUNIT ALPHA, MITOCHONDRIAL; 1. DR PANTHER; PTHR43380:SF1; 2-OXOISOVALERATE DEHYDROGENASE SUBUNIT ALPHA, MITOCHONDRIAL; 1. DR Pfam; PF00676; E1_dh; 1. DR Pfam; PF12573; OxoDH_E1alpha_N; 1. DR SUPFAM; SSF52518; Thiamin diphosphate-binding fold (THDP-binding); 1. DR PDBsum; 1QS0; -. DR PDBsum; 2BP7; -. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; Magnesium; Metal-binding; KW Oxidoreductase; Thiamine pyrophosphate. FT CHAIN 1..410 FT /note="2-oxoisovalerate dehydrogenase subunit alpha" FT /id="PRO_0000162249" FT BINDING 133 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000269|PubMed:10426958, FT ECO:0007744|PDB:1QS0" FT BINDING 134 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000269|PubMed:10426958, FT ECO:0007744|PDB:1QS0" FT BINDING 182 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000269|PubMed:10426958, FT ECO:0007744|PDB:1QS0" FT BINDING 213 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:10426958, FT ECO:0007744|PDB:1QS0" FT BINDING 214 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000269|PubMed:10426958, FT ECO:0007744|PDB:1QS0" FT BINDING 215 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000269|PubMed:10426958, FT ECO:0007744|PDB:1QS0" FT BINDING 242 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:10426958, FT ECO:0007744|PDB:1QS0" FT BINDING 242 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /evidence="ECO:0000269|PubMed:10426958, FT ECO:0007744|PDB:1QS0" FT BINDING 244 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:10426958, FT ECO:0007744|PDB:1QS0" FT MUTAGEN 313 FT /note="S->A: Does not affect activity with FT 3-methyl-2-oxobutanoate as substrate." FT /evidence="ECO:0000269|PubMed:8521848" FT MUTAGEN 315 FT /note="S->A: Does not affect activity with FT 3-methyl-2-oxobutanoate as substrate." FT /evidence="ECO:0000269|PubMed:8521848" FT MUTAGEN 319 FT /note="S->A: Does not affect activity with FT 3-methyl-2-oxobutanoate as substrate." FT /evidence="ECO:0000269|PubMed:8521848" FT HELIX 5..7 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 24..26 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 44..47 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 48..51 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 67..69 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 74..99 FT /evidence="ECO:0007829|PDB:1QS0" FT STRAND 102..104 FT /evidence="ECO:0007829|PDB:1QS0" FT TURN 110..112 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 113..122 FT /evidence="ECO:0007829|PDB:1QS0" FT STRAND 127..130 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 136..141 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 146..154 FT /evidence="ECO:0007829|PDB:1QS0" FT TURN 160..163 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 173..175 FT /evidence="ECO:0007829|PDB:1QS0" FT STRAND 182..185 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 186..200 FT /evidence="ECO:0007829|PDB:1QS0" FT STRAND 207..212 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 214..217 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 219..231 FT /evidence="ECO:0007829|PDB:1QS0" FT STRAND 235..241 FT /evidence="ECO:0007829|PDB:1QS0" FT STRAND 243..245 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 250..253 FT /evidence="ECO:0007829|PDB:1QS0" FT TURN 254..257 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 262..266 FT /evidence="ECO:0007829|PDB:1QS0" FT STRAND 270..275 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 279..294 FT /evidence="ECO:0007829|PDB:1QS0" FT STRAND 300..305 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 318..320 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 326..329 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 335..345 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 351..373 FT /evidence="ECO:0007829|PDB:1QS0" FT STRAND 378..380 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 388..390 FT /evidence="ECO:0007829|PDB:1QS0" FT STRAND 391..396 FT /evidence="ECO:0007829|PDB:1QS0" FT HELIX 399..406 FT /evidence="ECO:0007829|PDB:1QS0" SQ SEQUENCE 410 AA; 45268 MW; 0C998460CCFB9CF4 CRC64; MNEYAPLRLH VPEPTGRPGC QTDFSYLRLN DAGQARKPPV DVDAADTADL SYSLVRVLDE QGDAQGPWAE DIDPQILRQG MRAMLKTRIF DSRMVVAQRQ KKMSFYMQSL GEEAIGSGQA LALNRTDMCF PTYRQQSILM ARDVSLVEMI CQLLSNERDP LKGRQLPIMY SVREAGFFTI SGNLATQFVQ AVGWAMASAI KGDTKIASAW IGDGATAESD FHTALTFAHV YRAPVILNVV NNQWAISTFQ AIAGGESTTF AGRGVGCGIA SLRVDGNDFV AVYAASRWAA ERARRGLGPS LIEWVTYRAG PHSTSDDPSK YRPADDWSHF PLGDPIARLK QHLIKIGHWS EEEHQATTAE FEAAVIAAQK EAEQYGTLAN GHIPSAASMF EDVYKEMPDH LRRQRQELGV //