EzCatDB: M00190
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DB codeM00190
RLCP classification3.1177.805.87 : Transfer
CATH domainDomain 1-.-.-.-
Domain 22.40.50.100 : OB fold (Dihydrolipoamide Acetyltransferase, E2P)
Domain 32.40.50.100 : OB fold (Dihydrolipoamide Acetyltransferase, E2P)
Domain 44.10.320.10 : Dihydrolipoamide Transferase
Domain 53.30.559.10 : Chloramphenicol AcetyltransferaseCatalytic domain
E.C.2.3.1.12

CATH domainRelated 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 AcetyltransferaseM00188,M00189,T00223,M00191
4.10.320.10 : Dihydrolipoamide TransferaseM00188,M00189,T00223,M00191

Enzyme Name
UniProtKBKEGG

P10515
Protein nameDihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrialdihydrolipoyllysine-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
SynonymsEC 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
RefSeqNP_001922.2 (Protein)
NM_001931.4 (DNA/RNA sequence)
PfamPF00198 (2-oxoacid_dh)
PF00364 (Biotin_lipoyl)
PF02817 (E3_binding)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00010Glycolysis / Gluconeogenesis
MAP00020Citrate cycle (TCA cycle)
MAP00620Pyruvate metabolism

UniProtKB:Accession NumberP10515
Entry nameODP2_HUMAN
ActivityAcetyl-CoA + enzyme N(6)-(dihydrolipoyl)lysine = CoA + enzyme N(6)-(S-acetyldihydrolipoyl)lysine.
Subunit20 to 30 alpha(2)-beta(2) tetramers of E1 + 6 homodimers of E3 + 60 copies of E2.
Subcellular locationMitochondrion matrix.
CofactorBinds 2 lipoyl cofactors covalently.

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00010L00017C00024C15973
CompoundCoAEnzyme N(6)-(S-acetyldihydrolipoyl)lysineAcetyl-CoAEnzyme N(6)-(dihydrolipoyl)lysine
Typeamine group,carbohydrate,nucleotide,peptide/protein,sulfhydryl groupamide group,carbohydrate,lipid,peptide/protein,sulfhydryl group,sulfide groupamine group,carbohydrate,nucleotide,peptide/protein,sulfide groupamide group,lipid,peptide/protein,sulfhydryl group
ChEBI15346

15351

PubChem87642
6816

6302
444493

            
1fycAUnboundUnboundUnboundUnbound
1y8nBUnboundUnboundUnboundBound:LPA-LYS 173
1y8oBUnboundUnboundUnboundBound:LPA-LYS 173
1y8pBUnboundUnboundUnboundBound:LPA-LYS 173

Active-site residues
pdbCofactor-binding residues
         
1fycALYS  50(Lipoyl binding)
1y8nBLYS 173(Lipoyl binding)
1y8oBLYS 173(Lipoyl binding)
1y8pBLYS 173(Lipoyl binding)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Scheme I, p.3900-3901
[6]Fig.6, p.119-120

references
[1]
PubMed ID8471601
JournalBiochemistry
Year1993
Volume32
Pages3887-901
AuthorsMattevi A, Obmolova G, Kalk KH, Teplyakov A, Hol WG
TitleCrystallographic analysis of substrate binding and catalysis in dihydrolipoyl transacetylase (E2p).
[2]
PubMed ID8500617
JournalFEBS Lett
Year1993
Volume323
Pages243-6
AuthorsMachado RS, Guest JR, Williamson MP
TitleMobility in pyruvate dehydrogenase complexes with multiple lipoyl domains.
[3]
PubMed ID9729480
JournalBiochem J
Year1998
Volume334
Pages703-11
AuthorsJackson 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
TitleHeterologously expressed inner lipoyl domain of dihydrolipoyl acetyltransferase inhibits ATP-dependent inactivation of pyruvate dehydrogenase complex. Identification of important amino acid residues.
[4]
CommentsSTRUCTURE BY NMR OF 181-282.
Medline ID98323498
PubMed ID9649469
JournalGastroenterology
Year1998
Volume115
Pages139-46
AuthorsHoward MJ, Fuller C, Broadhurst RW, Perham RN, Tang JG, Quinn J, Diamond AG, Yeaman SJ
TitleThree-dimensional structure of the major autoantigen in primary biliary cirrhosis
Related PDB1fyc
Related UniProtKBP10515
[5]
PubMed ID10419491
JournalJ Biol Chem
Year1999
Volume274
Pages21769-75
AuthorsThelen JJ, Muszynski MG, David NR, Luethy MH, Elthon TE, Miernyk JA, Randall DD
TitleThe dihydrolipoamide S-acetyltransferase subunit of the mitochondrial pyruvate dehydrogenase complex from maize contains a single lipoyl domain.
[6]
PubMed ID11368334
JournalArch Biochem Biophys
Year2001
Volume386
Pages123-35
AuthorsLiu S, Gong X, Yan X, Peng T, Baker JC, Li L, Robben PM, Ravindran S, Andersson LA, Cole AB, Roche TE
TitleReaction mechanism for mammalian pyruvate dehydrogenase using natural lipoyl domain substrates.
[7]
PubMed ID11114246
JournalJ Mol Biol
Year2001
Volume305
Pages49-60
AuthorsJones DD, Stott KM, Reche PA, Perham RN
TitleRecognition of the lipoyl domain is the ultimate determinant of substrate channelling in the pyruvate dehydrogenase multienzyme complex.
[8]
PubMed ID12526798
JournalCell
Year2003
Volume112
Pages113-22
AuthorsJogl G, Tong L
TitleCrystal structure of carnitine acetyltransferase and implications for the catalytic mechanism and fatty acid transport.
[9]
PubMed ID15861126
JournalEMBO J
Year2005
Volume24
Pages1763-74
AuthorsKato M, Chuang JL, Tso SC, Wynn RM, Chuang DT
TitleCrystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complex.
Related PDB1y8n,1y8o,1y8n

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.

createdupdated
2002-12-012009-02-26


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Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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