DB code: M00190

RLCP classification 3.1177.805.87 : Transfer
CATH domain -.-.-.- :
2.40.50.100 : OB fold (Dihydrolipoamide Acetyltransferase, E2P)
2.40.50.100 : OB fold (Dihydrolipoamide Acetyltransferase, E2P)
4.10.320.10 : Dihydrolipoamide Transferase
3.30.559.10 : Chloramphenicol Acetyltransferase Catalytic domain
E.C. 2.3.1.12
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.40.50.100 : OB fold (Dihydrolipoamide Acetyltransferase, E2P) M00163 M00222 M00145 M00188 M00189 T00223 M00191 M00208
3.30.559.10 : Chloramphenicol Acetyltransferase M00188 M00189 T00223 M00191
4.10.320.10 : Dihydrolipoamide Transferase M00188 M00189 T00223 M00191

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P10515 Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
EC 2.3.1.12
70 kDa mitochondrial autoantigen of primary biliary cirrhosis
PBC
Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex
M2 antigen complex 70 kDa subunit
Pyruvate dehydrogenase complex component E2
PDC-E2
PDCE2
NP_001922.2 (Protein)
NM_001931.4 (DNA/RNA sequence)
PF00198 (2-oxoacid_dh)
PF00364 (Biotin_lipoyl)
PF02817 (E3_binding)
[Graphical View]

KEGG enzyme name
dihydrolipoyllysine-residue acetyltransferase
acetyl-CoA:dihydrolipoamide S-acetyltransferase
dihydrolipoamide S-acetyltransferase
dihydrolipoate acetyltransferase
dihydrolipoic transacetylase
dihydrolipoyl acetyltransferase
lipoate acetyltransferase
lipoate transacetylase
lipoic acetyltransferase
lipoic acid acetyltransferase
lipoic transacetylase
lipoylacetyltransferase
thioltransacetylase A
transacetylase X
enzyme-dihydrolipoyllysine:acetyl-CoA S-acetyltransferase
acetyl-CoA:enzyme 6-N-(dihydrolipoyl)lysine S-acetyltransferase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P10515 ODP2_HUMAN Acetyl-CoA + enzyme N(6)-(dihydrolipoyl)lysine = CoA + enzyme N(6)-(S-acetyldihydrolipoyl)lysine. 20 to 30 alpha(2)-beta(2) tetramers of E1 + 6 homodimers of E3 + 60 copies of E2. Mitochondrion matrix. Binds 2 lipoyl cofactors covalently.

KEGG Pathways
Map code Pathways E.C.
MAP00010 Glycolysis / Gluconeogenesis
MAP00020 Citrate cycle (TCA cycle)
MAP00620 Pyruvate metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00010 L00017 C00024 C15973
E.C.
Compound CoA Enzyme N(6)-(S-acetyldihydrolipoyl)lysine Acetyl-CoA Enzyme N(6)-(dihydrolipoyl)lysine
Type amine group,carbohydrate,nucleotide ,peptide/protein,sulfhydryl group amide group,carbohydrate,lipid,peptide/protein,sulfhydryl group,sulfide group nucleotide ,peptide/protein,sulfide group,amine group,carbohydrate amide group,lipid,peptide/protein,sulfhydryl group
ChEBI 15346
15351
PubChem 6816
87642
444493
6302
1fycA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1y8nB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:LPA-LYS_173
1y8oB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:LPA-LYS_173
1y8pB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:LPA-LYS_173

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1fycA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 50(Lipoyl binding)
1y8nB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 173(Lipoyl binding)
1y8oB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 173(Lipoyl binding)
1y8pB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 173(Lipoyl binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
Scheme I, p.3900-3901
[6]
Fig.6, p.119-120

References
[1]
Resource
Comments
Medline ID
PubMed ID 8471601
Journal Biochemistry
Year 1993
Volume 32
Pages 3887-901
Authors Mattevi A, Obmolova G, Kalk KH, Teplyakov A, Hol WG
Title Crystallographic analysis of substrate binding and catalysis in dihydrolipoyl transacetylase (E2p).
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8500617
Journal FEBS Lett
Year 1993
Volume 323
Pages 243-6
Authors Machado RS, Guest JR, Williamson MP
Title Mobility in pyruvate dehydrogenase complexes with multiple lipoyl domains.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9729480
Journal Biochem J
Year 1998
Volume 334
Pages 703-11
Authors Jackson JC, Vinluan CC, Dragland CJ, Sundararajan V, Yan B, Gounarides JS, Nirmala NR, Topiol S, Ramage P, Blume JE, Aicher TD, Bell PA, Mann WR
Title Heterologously expressed inner lipoyl domain of dihydrolipoyl acetyltransferase inhibits ATP-dependent inactivation of pyruvate dehydrogenase complex. Identification of important amino acid residues.
Related PDB
Related UniProtKB
[4]
Resource
Comments STRUCTURE BY NMR OF 181-282.
Medline ID 98323498
PubMed ID 9649469
Journal Gastroenterology
Year 1998
Volume 115
Pages 139-46
Authors Howard MJ, Fuller C, Broadhurst RW, Perham RN, Tang JG, Quinn J, Diamond AG, Yeaman SJ
Title Three-dimensional structure of the major autoantigen in primary biliary cirrhosis
Related PDB 1fyc
Related UniProtKB P10515
[5]
Resource
Comments
Medline ID
PubMed ID 10419491
Journal J Biol Chem
Year 1999
Volume 274
Pages 21769-75
Authors Thelen JJ, Muszynski MG, David NR, Luethy MH, Elthon TE, Miernyk JA, Randall DD
Title The dihydrolipoamide S-acetyltransferase subunit of the mitochondrial pyruvate dehydrogenase complex from maize contains a single lipoyl domain.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11368334
Journal Arch Biochem Biophys
Year 2001
Volume 386
Pages 123-35
Authors Liu S, Gong X, Yan X, Peng T, Baker JC, Li L, Robben PM, Ravindran S, Andersson LA, Cole AB, Roche TE
Title Reaction mechanism for mammalian pyruvate dehydrogenase using natural lipoyl domain substrates.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 11114246
Journal J Mol Biol
Year 2001
Volume 305
Pages 49-60
Authors Jones DD, Stott KM, Reche PA, Perham RN
Title Recognition of the lipoyl domain is the ultimate determinant of substrate channelling in the pyruvate dehydrogenase multienzyme complex.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 12526798
Journal Cell
Year 2003
Volume 112
Pages 113-22
Authors Jogl G, Tong L
Title Crystal structure of carnitine acetyltransferase and implications for the catalytic mechanism and fatty acid transport.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 15861126
Journal EMBO J
Year 2005
Volume 24
Pages 1763-74
Authors Kato M, Chuang JL, Tso SC, Wynn RM, Chuang DT
Title Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complex.
Related PDB 1y8n 1y8o 1y8n
Related UniProtKB

Comments
This enzyme is composed of the N-terminal mitochondrion region, two lipoyl-binding domains, E3-binding domain, and the C-terminal catalytic domain.
Although only the structure of the second lipoyl domain has been solved, the catalytic domain seems to be homologous to that of counterpart enzymes from bacteria (M00188 & M00189 in EzCatDB).
Although the lipoyl lysine has been identified as a cofactor in Swiss-prot data (P10515), it must be a substrate/product ligand.
This enzyme catalyzes transfer of acetyl group from lypoyllysine of the lipoyl-binding domain to sulfur atom of CoA.

Created Updated
2002-12-01 2009-02-26