DB code: T00210

CATH domain 3.40.50.970 : Rossmann fold
3.40.50.920 : Rossmann fold Catalytic domain
3.40.50.970 : Rossmann fold
E.C. 1.2.4.4
CSA 1dtw
M-CSA 1dtw
MACiE M0280

CATH domain Related DB codes (homologues)
3.40.50.970 : Rossmann fold T00237 T00230

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P12694 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial
EC 1.2.4.4
Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain
BCKDE1A
BCKDH E1-alpha
NP_000700.1 (Protein)
NM_000709.3 (DNA/RNA sequence)
PF00676 (E1_dh)
[Graphical View]
P21953 2-oxoisovalerate dehydrogenase subunit beta, mitochondrial
EC 1.2.4.4
Branched-chain alpha-keto acid dehydrogenase E1 component beta chain
BCKDE1B
BCKDH E1-beta
NP_000047.1 (Protein)
NM_000056.3 (DNA/RNA sequence)
NP_898871.1 (Protein)
NM_183050.2 (DNA/RNA sequence)
PF02779 (Transket_pyr)
PF02780 (Transketolase_C)
[Graphical View]

KEGG enzyme name
3-methyl-2-oxobutanoate dehydrogenase(2-methylpropanoyl-transferring)
2-oxoisocaproate dehydrogenase
2-oxoisovalerate (lipoate) dehydrogenase
3-methyl-2-oxobutanoate dehydrogenase (lipoamide)
3-methyl-2-oxobutanoate:lipoamide oxidoreductase (decarboxylatingand acceptor-2-methylpropanoylating)
alpha-keto-alpha-methylvalerate dehydrogenase
alpha-ketoisocaproate dehydrogenase
alpha-ketoisocaproic dehydrogenase
alpha-ketoisocaproic-alpha-keto-alpha-methylvaleric dehydrogenase
alpha-ketoisovalerate dehydrogenase
alpha-oxoisocaproate dehydrogenase
BCKDH
BCOAD
branched chain keto acid dehydrogenase
branched-chain (-2-oxoacid) dehydrogenase (BCD)
branched-chain 2-keto acid dehydrogenase
branched-chain 2-oxo acid dehydrogenase
branched-chain alpha-keto acid dehydrogenase
branched-chain alpha-oxo acid dehydrogenase
branched-chain keto acid dehydrogenase
branched-chain ketoacid dehydrogenase
dehydrogenase, 2-oxoisovalerate (lipoate)
dehydrogenase, branched chain alpha-keto acid

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P21953 ODBB_HUMAN 3-methyl-2-oxobutanoate + [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] lipoyllysine = [dihydrolipoyllysine-residue (2- methylpropanoyl)transferase] S-(2- methylpropanoyl)dihydrolipoyllysine + CO(2). Heterodimer of an alpha and a beta chain. Mitochondrion matrix.
P12694 ODBA_HUMAN 3-methyl-2-oxobutanoate + [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] lipoyllysine = [dihydrolipoyllysine-residue (2- methylpropanoyl)transferase] S-(2- methylpropanoyl)dihydrolipoyllysine + CO(2). Heterotetramer of alpha and beta chains. Mitochondrion matrix. Thiamine pyrophosphate.

KEGG Pathways
Map code Pathways E.C.
MAP00280 Valine, leucine and isoleucine degradation

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00068 C00141 L00015 C15977 C00011
E.C.
Compound Thiamine diphosphate 3-Methyl-2-oxobutanoate [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] lipoyllysine [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] S-(2-methylpropanoyl)dihydrolipoyllysine CO2
Type amine group,aromatic ring (with nitrogen atoms),phosphate group/phosphate ion carbohydrate,carboxyl group amide group,disulfide bond,lipid,peptide/protein amide group,carbohydrate,lipid,peptide/protein,sulfhydryl group,sulfide group others
ChEBI 9532
16530
16526
PubChem 1132
49
280
1dtwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:TDP Unbound Unbound Unbound Unbound
1olsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:TDP Unbound Unbound Unbound Unbound
1oluA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:TDP Unbound Unbound Unbound Unbound
1olxA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:TDP Unbound Unbound Unbound Unbound
1u5bA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:TDP Unbound Unbound Unbound Unbound
1v11A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:TDP Unbound Unbound Unbound Unbound
1v16A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:TDP Unbound Unbound Unbound Unbound
1v1mA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:TDP Unbound Unbound Unbound Unbound
1v1rA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1x7wA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:TDP Unbound Unbound Unbound Unbound
1x7xA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:TDP Unbound Unbound Unbound Unbound
1x7yA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:TDP Unbound Unbound Unbound Unbound
1x7zA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:TDP Unbound Unbound Unbound Unbound
1x80A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:TDP Unbound Unbound Unbound Unbound
1dtwB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1olsB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1oluB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1olxB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1u5bB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1v11B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1v16B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1v1mB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1v1rB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1x7wB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1x7xB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1x7yB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1x7zB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1x80B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1dtwB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1olsB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1oluB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1olxB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1u5bB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1v11B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1v16B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1v1mB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1v1rB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1x7wB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1x7xB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1x7yB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1x7zB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1x80B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [23], [27]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1dtwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 291 ;SER 161;PRO 163;THR 166;GLN 167(Potassium-1);GLU 193;ASN 222;TYR 224(Magnesium) SER 292; (Phospholylated) invisible 302-313
1olsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 291 GLN 112;SER 161;PRO 163;THR 166;GLN 167(Potassium-1);GLU 193;ASN 222;TYR 224(Magnesium) SER 292; (Phospholylated) invisible 293-294, 299, 302-307
1oluA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 112;SER 161;PRO 163;THR 166;GLN 167(Potassium-1);GLU 193;ASN 222;TYR 224(Magnesium) ; (Phospholylated) mutant H291A, invisible 288-312
1olxA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 291 GLN 112;SER 161;PRO 163;THR 166;GLN 167(Potassium-1);GLU 193;ASN 222;TYR 224(Magnesium) SER 292; (Phospholylated) invisible 302-306
1u5bA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 291 ;SER 161;PRO 163;THR 166;GLN 167(Potassium-1);GLU 193;ASN 222;TYR 224(Magnesium) SER 292; (Phospholylated) invisible 302-305
1v11A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 112;SER 161;PRO 163;THR 166;GLN 167(Potassium-1);GLU 193;ASN 222;TYR 224(Magnesium) ; (Phospholylated) mutant R287A, invisible 289-312
1v16A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 112;SER 161;PRO 163;THR 166;GLN 167(Potassium-1);GLU 193;ASN 222;TYR 224(Magnesium) ; (Phospholylated) mutant Y300F, invisible 289-312
1v1mA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 112;SER 161;PRO 163;THR 166;GLN 167(Potassium-1);GLU 193;ASN 222;TYR 224(Magnesium) ; (Phospholylated) invisible 290-312
1v1rA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 112;SER 161;PRO 163;THR 166;GLN 167(Potassium-1);GLU 193;ASN 222; (Magnesium) ; (Phospholylated) invisible 223-230, 287-313
1x7wA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 112;SER 161;PRO 163;THR 166;GLN 167(Potassium-1);GLU 193;ASN 222;TYR 224(Magnesium) ; (Phospholylated) mutant S292Q, invisible 288-312
1x7xA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 112;SER 161;PRO 163;THR 166;GLN 167(Potassium-1);GLU 193;ASN 222;TYR 224(Magnesium) ; (Phospholylated) mutant S292E, invisible 288-312
1x7yA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 112;SER 161;PRO 163;THR 166;GLN 167(Potassium-1);GLU 193;ASN 222;TYR 224(Magnesium) ; (Phospholylated) mutant S292N, invisible 288-312
1x7zA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 291 GLN 112;SER 161;PRO 163;THR 166;GLN 167(Potassium-1);GLU 193;ASN 222;TYR 224(Magnesium) ; (Phospholylated) mutant S292D, invisible 302-305
1x80A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLN 112;SER 161;PRO 163;THR 166;GLN 167(Potassium-1);GLU 193;ASN 222;TYR 224(Magnesium) ; (Phospholylated) invisible 288-312
1dtwB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1olsB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1oluB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1olxB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1u5bB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1v11B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1v16B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1v1mB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1v1rB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1x7wB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1x7xB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1x7yB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1x7zB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1x80B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1dtwB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 76;HIS 146 GLY 128;LEU 130;THR 131;CYS 178;ASP 181;ASN 183(Potassium-2)
1olsB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 76;HIS 146 GLY 128;LEU 130;THR 131;CYS 178;ASP 181;ASN 183(Potassium-2)
1oluB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 76;HIS 146 GLY 128;LEU 130;THR 131;CYS 178;ASP 181;ASN 183(Potassium-2)
1olxB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 76; GLY 128;LEU 130;THR 131;CYS 178;ASP 181;ASN 183(Potassium-2) mutant H146A
1u5bB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 76;HIS 146 GLY 128;LEU 130;THR 131;CYS 178;ASP 181;ASN 183(Potassium-2)
1v11B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 76;HIS 146 GLY 128;LEU 130;THR 131;CYS 178;ASP 181;ASN 183(Potassium-2)
1v16B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 76;HIS 146 GLY 128;LEU 130;THR 131;CYS 178;ASP 181;ASN 183(Potassium-2)
1v1mB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 76;HIS 146 GLY 128;LEU 130;THR 131;CYS 178;ASP 181;ASN 183(Potassium-2)
1v1rB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 76;HIS 146 GLY 128;LEU 130;THR 131;CYS 178;ASP 181;ASN 183(Potassium-2)
1x7wB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 76;HIS 146 GLY 128;LEU 130;THR 131;CYS 178;ASP 181;ASN 183(Potassium-2)
1x7xB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 76;HIS 146 GLY 128;LEU 130;THR 131;CYS 178;ASP 181;ASN 183(Potassium-2)
1x7yB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 76;HIS 146 GLY 128;LEU 130;THR 131;CYS 178;ASP 181;ASN 183(Potassium-2)
1x7zB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 76;HIS 146 GLY 128;LEU 130;THR 131;CYS 178;ASP 181;ASN 183(Potassium-2)
1x80B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 76;HIS 146 GLY 128;LEU 130;THR 131;CYS 178;ASP 181;ASN 183(Potassium-2)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Fig.1
[4]
Fig.1, Scheme I, p.8508-8510
[8]
[12]
Fig.1
[13]
Fig.1, p.181-185
[15]
p.787-789
[21]
Fig.2
[23]
p.4170-4171
[24]
p.50
[26]
Fig.4, p.6999-7001
[27]
Fig.7, p.43407-43409
[29]
Fig.8, p.1028-1029

References
[1]
Resource
Comments
Medline ID
PubMed ID 6510417
Journal Eur J Biochem
Year 1984
Volume 145
Pages 587-91
Authors Cook KG, Bradford AP, Yeaman SJ, Aitken A, Fearnley IM, Walker JE
Title Regulation of bovine kidney branched-chain 2-oxoacid dehydrogenase complex by reversible phosphorylation.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2699393
Journal Ann N Y Acad Sci
Year 1989
Volume 573
Pages 1-20
Authors Perham RN, Packman LC
Title 2-Oxo acid dehydrogenase multienzyme complexes: domains, dynamics, and design.
Related PDB
Related UniProtKB
[3]
Resource
Comments VARIANT MSUD ASN-438
Medline ID 89198104
PubMed ID 2703538
Journal J Clin Invest
Year 1989
Volume 83
Pages 1425-9
Authors Zhang B, Edenberg HJ, Crabb DW, Harris RA
Title Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease.
Related PDB
Related UniProtKB P12694
[4]
Resource
Comments
Medline ID
PubMed ID 1888719
Journal Biochemistry
Year 1991
Volume 30
Pages 8501-12
Authors Perham RN
Title Domains, motifs, and linkers in 2-oxo acid dehydrogenase multienzyme complexes: a paradigm in the design of a multifunctional protein.
Related PDB
Related UniProtKB
[5]
Resource
Comments VARIANT MSUD ARG-206
Medline ID 94060128
PubMed ID 8161368
Journal Biochim Biophys Acta
Year 1993
Volume 1225
Pages 64-70
Authors Nobukuni Y, Mitsubuchi H, Hayashida Y, Ohta K, Indo Y, Ichiba Y, Endo F, Matsuda I
Title Heterogeneity of mutations in maple syrup urine disease (MSUD): screening and identification of affected E1 alpha and E1 beta subunits of the branched-chain alpha-keto-acid dehydrogenase multienzyme complex.
Related PDB
Related UniProtKB P21953
[6]
Resource
Comments
Medline ID
PubMed ID 8262228
Journal FEBS Lett
Year 1993
Volume 336
Pages 197-200
Authors Bunik V, Follmann H
Title Thioredoxin reduction dependent on alpha-ketoacid oxidation by alpha-ketoacid dehydrogenase complexes.
Related PDB
Related UniProtKB
[7]
Resource
Comments VARIANT MSUD CYS-413
Medline ID 94311310
PubMed ID 8037208
Journal Am J Hum Genet
Year 1994
Volume 55
Pages 297-304
Authors Chuang JL, Fisher CR, Cox RP, Chuang DT
Title Molecular basis of maple syrup urine disease: novel mutations at the E1 alpha locus that impair E1(alpha 2 beta 2) assembly or decrease steady-state E1 alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase complex.
Related PDB
Related UniProtKB P12694
[8]
Resource
Comments
Medline ID
PubMed ID 8537366
Journal J Biol Chem
Year 1995
Volume 270
Pages 31071-6
Authors Hawes JW, Schnepf RJ, Jenkins AE, Shimomura Y, Popov KM, Harris RA
Title Roles of amino acid residues surrounding phosphorylation site 1 of branched-chain alpha-ketoacid dehydrogenase (BCKDH) in catalysis and phosphorylation site recognition by BCKDH kinase.
Related PDB
Related UniProtKB
[9]
Resource
Comments VARIANTS MSUD ARG-290 AND CYS-409
Medline ID 95190052
PubMed ID 7883996
Journal J Clin Invest
Year 1995
Volume 95
Pages 954-63
Authors Chuang JL, Davie JR, Chinsky JM, Wynn RM, Cox RP, Chuang DT
Title Molecular and biochemical basis of intermediate maple syrup urine disease. Occurrence of homozygous G245R and F364C mutations at the E1 alpha locus of Hispanic-Mexican patients.
Related PDB
Related UniProtKB P12694
[10]
Resource
Comments
Medline ID
PubMed ID 7651225
Journal Methods Enzymol
Year 1995
Volume 251
Pages 436-48
Authors Perham RN
Title Structure and posttranslational modification of lipoyl domain of 2-oxo-acid dehydrogenase multienzyme complexes.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 9381974
Journal Adv Enzyme Regul
Year 1997
Volume 37
Pages 271-93
Authors Harris RA, Hawes JW, Popov KM, Zhao Y, Shimomura Y, Sato J, Jaskiewicz J, Hurley TD
Title Studies on the regulation of the mitochondrial alpha-ketoacid dehydrogenase complexes and their kinases.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 9278141
Journal Biol Chem
Year 1997
Volume 378
Pages 617-34
Authors Berg A, de Kok A
Title 2-Oxo acid dehydrogenase multienzyme complexes. The central role of the lipoyl domain.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 9655906
Journal Biochim Biophys Acta
Year 1998
Volume 1385
Pages 177-86
Authors Schellenberger A
Title Sixty years of thiamin diphosphate biochemistry.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 10187830
Journal J Biol Chem
Year 1999
Volume 274
Pages 10405-12
Authors Huang YS, Chuang DT
Title Mechanisms for GroEL/GroES-mediated folding of a large 86-kDa fusion polypeptide in vitro.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 10426958
Journal Nat Struct Biol
Year 1999
Volume 6
Pages 785-92
Authors Aevarsson A, Seger K, Turley S, Sokatch JR, Hol WG
Title Crystal structure of 2-oxoisovalerate and dehydrogenase and the architecture of 2-oxo acid dehydrogenase multienzyme complexes.
Related PDB 1qs0
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 10644743
Journal J Biol Chem
Year 2000
Volume 275
Pages 2786-94
Authors Wynn RM, Song JL, Chuang DT
Title GroEL/GroES promote dissociation/reassociation cycles of a heterodimeric intermediate during alpha(2)beta(2) protein assembly. Iterative annealing at the quaternary structure level.
Related PDB
Related UniProtKB
[17]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 46-445 IN COMPLEX WITH THIAMINE PYROPHOSPHATE AND POTASSIUM IONS, AND SUBUNIT STRUCTURE.
Medline ID
PubMed ID 10745006
Journal Structure Fold Des
Year 2000
Volume 8
Pages 277-91
Authors Aevarsson A, Chuang JL, Wynn RM, Turley S, Chuang DT, Hol WG
Title Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease.
Related PDB 1dtw
Related UniProtKB P12694
[18]
Resource
Comments
Medline ID
PubMed ID 11509994
Journal Am J Hum Genet
Year 2001
Volume 69
Pages 863-8
Authors Edelmann L, Wasserstein MP, Kornreich R, Sansaricq C, Snyderman SE, Diaz GA
Title Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 11395405
Journal Annu Rev Biochem
Year 2001
Volume 70
Pages 149-80
Authors Huang X, Holden HM, Raushel FM
Title Channeling of substrates and intermediates in enzyme-catalyzed reactions.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 11168412
Journal Eur J Biochem
Year 2001
Volume 268
Pages 727-36
Authors Ono K, Hakozaki M, Suzuki T, Mori T, Hata H, Kochi H
Title cDNA cloning of the chicken branched-chain alpha-keto acid dehydrogenase complex. Chicken-specific residues of the acyltransferase affect the overall activity and the interaction with the dehydrogenase.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 11477096
Journal J Biol Chem
Year 2001
Volume 276
Pages 38329-36
Authors Reed LJ
Title A trail of research from lipoic acid to alpha-keto acid dehydrogenase complexes.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 11507102
Journal J Biol Chem
Year 2001
Volume 276
Pages 40241-6
Authors Song JL, Chuang DT
Title Natural osmolyte trimethylamine N-oxide corrects assembly defects of mutant branched-chain alpha-ketoacid decarboxylase in maple syrup urine disease.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11069910
Journal J Biol Chem
Year 2001
Volume 276
Pages 4168-74
Authors Wynn RM, Ho R, Chuang JL, Chuang DT
Title Roles of active site and novel K+ ion-binding site residues in human mitochondrial branched-chain alpha-ketoacid decarboxylase/dehydrogenase.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 12023822
Journal Biochem Soc Trans
Year 2002
Volume 30
Pages 47-51
Authors Perham RN, Jones DD, Chauhan HJ, Howard MJ
Title Substrate channelling in 2-oxo acid dehydrogenase multienzyme complexes.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 12383259
Journal Eur J Biochem
Year 2002
Volume 269
Pages 5004-15
Authors Bunik VI, Sievers C
Title Inactivation of the 2-oxo acid dehydrogenase complexes upon generation of intrinsic radical species.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 12795594
Journal Biochemistry
Year 2003
Volume 42
Pages 6996-7002
Authors Fries M, Jung HI, Perham RN
Title Reaction mechanism of the heterotetrameric (alpha2beta2) E1 component of 2-oxo acid dehydrogenase multienzyme complexes.
Related PDB
Related UniProtKB
[27]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12902323
Journal J Biol Chem
Year 2003
Volume 278
Pages 43402-10
Authors Wynn RM, Machius M, Chuang JL, Li J, Tomchick DR, Chuang DT
Title Roles of His291-alpha and His146-beta' in the reductive acylation reaction catalyzed by human branched-chain alpha-ketoacid dehydrogenase: refined phosphorylation loop structure in the active site.
Related PDB 1ols 1olu 1olx
Related UniProtKB
[28]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15166214
Journal J Biol Chem
Year 2004
Volume 279
Pages 32968-78
Authors Li J, Wynn RM, Machius M, Chuang JL, Karthikeyan S, Tomchick DR, Chuang DT
Title Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase.
Related PDB 1v11 1v16 1v1m 1v1r
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 15033367
Journal J Mol Biol
Year 2004
Volume 337
Pages 1011-33
Authors Nakai T, Nakagawa N, Maoka N, Masui R, Kuramitsu S, Kamiya N
Title Ligand-induced conformational changes and a reaction intermediate in branched-chain 2-oxo acid dehydrogenase (E1) from Thermus thermophilus HB8, as revealed by X-ray crystallography.
Related PDB
Related UniProtKB
[30]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15576032
Journal Structure (Camb)
Year 2004
Volume 12
Pages 2185-96
Authors Wynn RM, Kato M, Machius M, Chuang JL, Li J, Tomchick DR, Chuang DT
Title Molecular mechanism for regulation of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase complex by phosphorylation.
Related PDB 1u5b 1x7w 1x7x 1x7y 1x7z 1x80
Related UniProtKB

Comments
Although this enzyme complex binds magnesium and potassium ions, they are not involved in catalysis.
One of the substrates for this enzyme seems to be a modified lysine residue, lipoyllysine, of dihydrolipoyllysine-residue (2-methylpropanoyl)transferase, or E2 component (E.C. 2.3.1.168; ODB2_HUMAN;P11182).
This enzyme is called branched-chain alpha-keto acid dehydrogenase E1 component.
The following enzymes form multienzyme complex:
pyruvate decarboxylase (E1p, EC 1.2.4.1)
2-oxoglutarate decarboxylase (E1o, EC 1.2.4.2)
dihydrolipoyl acetyltransferase (E2p, EC 2.3.1.12)
dihydrolipoyl succinyltransferase (E2o, EC 2.3.1.61)
dihydrolipoamide dehydrogenase (E3, EC 1.6.4.3)
dihydrolipoyl dehydrogenase (E3, EC 1.8.1.4)
According to the literature [25], [26] and [28], this enzyme catalyzes the following reactions:
(A) Addition of thiazole ring of thiamine diphosphate (ThDP) to carbonyl carbon of the substrate, 3-Methyl-2-oxobutanoate, forming tetrahedral intermediate:
(B) Elimination of CO2, leading to alpha-carbanion/enamine intermediate:
(C) Transfer of sulfur atom from the other sulfur atom of disulfide bond of lipoyllysine to the carbanion, forming the second tetrahedral intermediate:
(D) Elimination of product, S-(2-methylpropanoyl)dihydrolipoyllysine, from ThDP:

Created Updated
2004-03-25 2009-02-26