DB code: M00191

CATH domain	2.40.50.100 : OB fold (Dihydrolipoamide Acetyltransferase, E2P)
	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 M00190 M00208
3.30.559.10 : Chloramphenicol Acetyltransferase	M00188 M00189 T00223 M00190
4.10.320.10 : Dihydrolipoamide Transferase	M00188 M00189 T00223 M00190

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	RefSeq	Pfam
P06959	Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex	EC 2.3.1.12 Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex E2	NP_414657.1 (Protein) NC_000913.2 (DNA/RNA sequence) YP_488418.1 (Protein) NC_007779.1 (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
P06959	ODP2_ECOLI	Acetyl-CoA + enzyme N(6)-(dihydrolipoyl)lysine = CoA + enzyme N(6)-(S-acetyldihydrolipoyl)lysine.	Forms a 24-polypeptide structural core with octahedral symmetry.		Binds 3 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	amine group,carbohydrate,nucleotide ,peptide/protein,sulfide group	amide group,lipid,peptide/protein,sulfhydryl group
ChEBI						15346 15346		15351 15351
PubChem						6816 87642 6816 87642		444493 6302 444493 6302
1qjoA						Unbound	Unbound	Unbound	Unbound

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
1qjoA							LYS 41(Lipolyl binding)

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[13]	p.1547
[14]	Scheme I, p.3899-3901
[17]	p.1194-1195
[20]	Fig.1, p.4292-4295
[32]	Fig.6

References
[1]
Resource
Comments
Medline ID
PubMed ID	389239
Journal	Biochem Biophys Res Commun
Year	1979
Volume	90
Pages	431-8
Authors	Fuller CC, Reed LJ, Oliver RM, Hackert ML
Title	Crystallization of a dihydrolipoyl transacetylase--dihydrolipoyl dehydrogenase subcomplex and its implications regarding the subunit structure of the pyruvate dehydrogenase complex from Escherichia coli.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID	6376124
Journal	Eur J Biochem
Year	1984
Volume	141
Pages	361-74
Authors	Spencer ME, Darlison MG, Stephens PE, Duckenfield IK, Guest JR
Title	Nucleotide sequence of the sucB gene encoding the dihydrolipoamide succinyltransferase of Escherichia coli K12 and homology with the corresponding acetyltransferase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID	3101735
Journal	Biochemistry
Year	1986
Volume	25
Pages	8173-8
Authors	Yang YS, Frey PA
Title	Dihydrolipoyl transacetylase of Escherichia coli. Formation of 8-S-acetyldihydrolipoamide.
Related PDB
Related UniProtKB
[4]
Resource
Comments	LIPOYL DOMAIN CONFORMATION.
Medline ID	89052887
PubMed ID	3191993
Journal	FEBS Lett
Year	1988
Volume	240
Pages	205-10
Authors	Hanemaaijer R, Vervoort J, Westphal AH, de Kok A, Veeger C
Title	Mobile sequences in the pyruvate dehydrogenase complex, the E2 component, the catalytic domain and the 2-oxoglutarate dehydrogenase complex of Azotobacter vinelandii, as detected by 600 MHz 1H-NMR spectroscopy.
Related PDB
Related UniProtKB	P10802
[5]
Resource
Comments
Medline ID
PubMed ID	2271545
Journal	Biochemistry
Year	1990
Volume	29
Pages	8614-9
Authors	Niu XD, Stoops JK, Reed LJ
Title	Overexpression and mutagenesis of the catalytic domain of dihydrolipoamide acetyltransferase from Saccharomyces cerevisiae.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID	2192914
Journal	FEBS Lett
Year	1990
Volume	264
Pages	206-10
Authors	Dardel F, Packman LC, Perham RN
Title	Expression in Escherichia coli of a sub-gene encoding the lipoyl domain of the pyruvate dehydrogenase complex of Bacillus stearothermophilus.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID	1908777
Journal	Eur J Biochem
Year	1991
Volume	200
Pages	29-34
Authors	Schulze E, Benen JA, Westphal AH, de Kok A
Title	Interaction of lipoamide dehydrogenase with the dihydrolipoyl transacetylase component of the pyruvate dehydrogenase complex from Azotobacter vinelandii.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID	1935951
Journal	Eur J Biochem
Year	1991
Volume	201
Pages	561-8
Authors	Schulze E, Westphal AH, Obmolova G, Mattevi A, Hol WG, de Kok A
Title	The catalytic domain of the dihydrolipoyl transacetylase component of the pyruvate dehydrogenase complex from Azotobacter vinelandii and Escherichia coli. Expression, purification, properties and preliminary X-ray analysis.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID	1590756
Journal	Biochem J
Year	1992
Volume	283
Pages	665-71
Authors	Hipps DS, Perham RN
Title	Expression in Escherichia coli of a sub-gene encoding the lipoyl and peripheral subunit-binding domains of the dihydrolipoamide acetyltransferase component of the pyruvate dehydrogenase complex of Bacillus stearothermophilus.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID	1730230
Journal	Eur J Biochem
Year	1992
Volume	203
Pages	245-50
Authors	Snoep JL, Westphal AH, Benen JA, Teixeira de Mattos MJ, Neijssel OM, de Kok A
Title	Isolation and characterisation of the pyruvate dehydrogenase complex of anaerobically grown Enterococcus faecalis NCTC 775.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID	1429691
Journal	J Biol Chem
Year	1992
Volume	267
Pages	23484-8
Authors	Green JD, Perham RN, Ullrich SJ, Appella E
Title	Conformational studies of the interdomain linker peptides in the dihydrolipoyl acetyltransferase component of the pyruvate dehydrogenase multienzyme complex of Escherichia coli.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID	1589018
Journal	Nature
Year	1992
Volume	357
Pages	196-7
Authors	DeRosier DJ
Title	Enzyme complexes. A farewell to arms.
Related PDB
Related UniProtKB
[13]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 381-637.
Medline ID	92196586
PubMed ID	1549782
Journal	Science
Year	1992
Volume	255
Pages	1544-50
Authors	Mattevi A, Obmolova G, Schulze E, Kalk KH, Westphal AH, de Kok A, Hol WG
Title	Atomic structure of the cubic core of the pyruvate dehydrogenase multienzyme complex.
Related PDB	1eaa 1eab 1eac 1ead 1eae 1eaf
Related UniProtKB	P10802
[14]
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
[15]
Resource
Comments
Medline ID
PubMed ID	8436118
Journal	Eur J Biochem
Year	1993
Volume	211
Pages	591-9
Authors	Schulze E, Westphal AH, Hanemaaijer R, de Kok A
Title	Structure/function relationships in the pyruvate dehydrogenase complex from Azotobacter vinelandii. Role of the linker region between the binding and catalytic domain of the dihydrolipoyl transacetylase component.
Related PDB
Related UniProtKB
[16]
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
[17]
Resource
Comments	X-ray crystallography
Medline ID
PubMed ID	8487300
Journal	J Mol Biol
Year	1993
Volume	230
Pages	1183-99
Authors	Mattevi A, Obmolova G, Kalk KH, Westphal AH, de Kok A, Hol WG
Title	Refined crystal structure of the catalytic domain of dihydrolipoyl transacetylase (E2p) from Azotobacter vinelandii at 2.6 A resolution.
Related PDB	1dpb 1dpc 1dpd
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID	8433963
Journal	Protein Eng
Year	1993
Volume	6
Pages	101-8
Authors	Turner SL, Russell GC, Williamson MP, Guest JR
Title	Restructuring an interdomain linker in the dihydrolipoamide acetyltransferase component of the pyruvate dehydrogenase complex of Escherichia coli.
Related PDB
Related UniProtKB
[19]
Resource
Comments	STRUCTURE BY NMR OF 1-78.
Medline ID	94222112
PubMed ID	8068086
Journal	Eur J Biochem
Year	1994
Volume	221
Pages	87-100
Authors	Berg A, de Kok A, Vervoort J
Title	Sequential 1H and 15N nuclear magnetic resonance assignments and secondary structure of the N-terminal lipoyl domain of the dihydrolipoyl transacetylase component of the pyruvate dehydrogenase complex from Azotobacter vinelandii.
Related PDB
Related UniProtKB	P10802
[20]
Resource
Comments
Medline ID
PubMed ID	7703242
Journal	Biochemistry
Year	1995
Volume	34
Pages	4287-98
Authors	Hendle J, Mattevi A, Westphal AH, Spee J, de Kok A, Teplyakov A, Hol WG
Title	Crystallographic and enzymatic investigations on the role of Ser558, His610, and Asn614 in the catalytic mechanism of Azotobacter vinelandii dihydrolipoamide acetyltransferase (E2p).
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID	8918601
Journal	J Mol Biol
Year	1996
Volume	263
Pages	463-74
Authors	Wallis NG, Allen MD, Broadhurst RW, Lessard IA, Perham RN
Title	Recognition of a surface loop of the lipoyl domain underlies substrate channelling in the pyruvate dehydrogenase multienzyme complex.
Related PDB
Related UniProtKB
[22]
Resource
Comments	STRUCTURE BY NMR OF 1-78.
Medline ID	97234563
PubMed ID	9119000
Journal	Eur J Biochem
Year	1997
Volume	244
Pages	352-60
Authors	Berg A, Vervoort J, de Kok A
Title	Three-dimensional structure in solution of the N-terminal lipoyl domain of the pyruvate dehydrogenase complex from Azotobacter vinelandii.
Related PDB	1iyu 1iyv
Related UniProtKB	P10802
[23]
Resource
Comments
Medline ID
PubMed ID	9280309
Journal	FEBS Lett
Year	1997
Volume	413
Pages	339-43
Authors	Allen MD, Perham RN
Title	The catalytic domain of dihydrolipoyl acetyltransferase from the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus. Expression, purification and reversible denaturation.
Related PDB
Related UniProtKB
[24]
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
[25]
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
[26]
Resource
Comments
Medline ID
PubMed ID	10653630
Journal	Biochemistry
Year	2000
Volume	39
Pages	872-9
Authors	Spector S, Wang M, Carp SA, Robblee J, Hendsch ZS, Fairman R, Tidor B, Raleigh DP
Title	Rational modification of protein stability by the mutation of charged surface residues.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID	10735853
Journal	J Bacteriol
Year	2000
Volume	182
Pages	2119-24
Authors	Stein A, Firshein W
Title	Probable identification of a membrane-associated repressor of Bacillus subtilis DNA replication as the E2 subunit of the pyruvate dehydrogenase complex.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID	10913250
Journal	Biochemistry
Year	2000
Volume	39
Pages	8448-59
Authors	Jones DD, Stott KM, Howard MJ, Perham RN
Title	Restricted motion of the lipoyl-lysine swinging arm in the pyruvate dehydrogenase complex of Escherichia coli.
Related PDB	1qjo
Related UniProtKB
[29]
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
[30]
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
[31]
Resource
Comments
Medline ID
PubMed ID	12173931
Journal	Biochemistry
Year	2002
Volume	41
Pages	10446-53
Authors	Jung HI, Cooper A, Perham RN
Title	Identification of key amino acid residues in the assembly of enzymes into the pyruvate dehydrogenase complex of Bacillus stearothermophilus: a kinetic and thermodynamic analysis.
Related PDB
Related UniProtKB
[32]
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

Comments

This enzyme is Dihydrolipoyllysine-residue acetyltransferase, E2 component of pyruvate dehydrogenase complex. The pyruvate dehydrogenase complex is composed of pyruvate dehydrogenaes (E1 component; E.C. 1.2.4.1), dihydrolipoyllysine S-acetyltransferase (E2 component; E.C. 2.3.1.12), and lipoamide dehydrogenase (E3 component; E.C. 1.8.1.4). (The E3 component corresponds to the entry T00017 in EzCatDB.) This enzyme is composed of three N-terminal lipoyl-binding domains, E1/E3-binding domain, and the C-terminal catalytic domain. Although this enzyme has the same domain composition as that of its homologue (M00189 in EzCatDB), the catalytic residues are slightly different from those of the homologue. (The structure of the catalytic domain of this enzyme has not been solved yet.) This enzyme catalyzes transfer of acetyl group from lypoyllysine of the lipoyl-binding domain to thiol group of CoA. Although the structure of the catalytic domain has not been solved yet, it seems to be homologous to that of its counterpart enzymes from Bacillus stearothermophilus (M00188 in EzCatDB) and human (M00190 in EzCatDB). Moreover, the catalytic residues are nearly conserved, except for Arginine residue (Arg202 of M00188 in EzCatDB).

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