DB code: M00188

RLCP classification 3.1177.805.87 : Transfer
CATH domain 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 M0106

CATH domain Related DB codes (homologues)
2.40.50.100 : OB fold (Dihydrolipoamide Acetyltransferase, E2P) M00163 M00222 M00145 M00189 T00223 M00190 M00191 M00208
3.30.559.10 : Chloramphenicol Acetyltransferase M00189 T00223 M00190 M00191
4.10.320.10 : Dihydrolipoamide Transferase M00189 T00223 M00190 M00191

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
P11961 Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex
EC 2.3.1.12
E2
Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex
PF00198 (2-oxoacid_dh)
PF00364 (Biotin_lipoyl)
PF02817 (E3_binding)
[Graphical View]

KEGG enzyme name
dihydrolipoic transacetylase
dihydrolipoyllysine-residue acetyltransferase
acetyl-CoA:dihydrolipoamide S-acetyltransferase
dihydrolipoamide S-acetyltransferase
dihydrolipoate acetyltransferase
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
P11961 ODP2_BACST Acetyl-CoA + enzyme N(6)-(dihydrolipoyl)lysine = CoA + enzyme N(6)-(S-acetyldihydrolipoyl)lysine. Forms a 60-polypeptide structural core with icosahedral symmetry. Binds 1 lipoyl cofactor 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
1labA Unbound Unbound Unbound Unbound
1lacA Unbound Unbound Unbound Unbound
1ebdC Unbound Unbound Unbound Unbound
1w3dA Unbound Unbound Unbound Unbound
1w4eA Unbound Unbound Unbound Unbound
1w4fA Unbound Unbound Unbound Unbound
1w4gA Unbound Unbound Unbound Unbound
1w85I Unbound Unbound Unbound Unbound
1w85J Unbound Unbound Unbound Unbound
1w88I Unbound Unbound Unbound Unbound
1w88J Unbound Unbound Unbound Unbound
2pddA Unbound Unbound Unbound Unbound
1b5sA Unbound Unbound Unbound Unbound
1b5sB Unbound Unbound Unbound Unbound
1b5sC Unbound Unbound Unbound Unbound
1b5sD Unbound Unbound Unbound Unbound
1b5sE Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
PDB;1fyc, 1iyu, 1lab

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1labA LYS 42(Lipoyl binding)
1lacA LYS 42(Lipoyl binding)
1ebdC
1w3dA
1w4eA
1w4fA
1w4gA
1w85I
1w85J
1w88I
1w88J
2pddA
1b5sA ARG 206;THR 346;HIS 398;ASP 402 HIS 398
1b5sB ARG 206;THR 346;HIS 398;ASP 402 HIS 398
1b5sC ARG 206;THR 346;HIS 398;ASP 402 HIS 398
1b5sD ARG 206;THR 346;HIS 398;ASP 402 HIS 398
1b5sE ARG 206;THR 346;HIS 398;ASP 402 HIS 398

References for Catalytic Mechanism
References Sections No. of steps in catalysis

References
[1]
Resource
Comments
Medline ID
PubMed ID 6345153
Journal Eur J Biochem
Year 1983
Volume 133
Pages 481-9
Authors Stephens PE, Darlison MG, Lewis HM, Guest JR
Title The pyruvate dehydrogenase complex of Escherichia coli K12. Nucleotide sequence encoding the dihydrolipoamide acetyltransferase component
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 6090132
Journal Eur J Biochem
Year 1984
Volume 143
Pages 561-6
Authors Schrenk DF, Bisswanger H
Title Measurements of electron spin resonance with the pyruvate dehydrogenase complex from Escherichia coli. Studies on the allosteric binding site of acetyl-coenzyme A
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 3903169
Journal J Mol Biol
Year 1985
Volume 185
Pages 743-54
Authors Guest JR, Lewis HM, Graham LD, Packman LC, Perham RN
Title Genetic reconstruction and functional analysis of the repeating lipoyl domains in the pyruvate dehydrogenase multienzyme complex of Escherichia coli
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 3691494
Journal Eur J Biochem
Year 1987
Volume 169
Pages 245-52
Authors Hanemaaijer R, de Kok A, Jolles J, Veeger C
Title The domain structure of the dihydrolipoyl transacetylase component of the pyruvate dehydrogenase complex from Azotobacter vinelandii.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 2917567
Journal Eur J Biochem
Year 1989
Volume 179
Pages 287-92
Authors Hanemaaijer R, Westphal AH, Van Der Heiden T, De Kok A, Veeger C
Title The quaternary structure of the dihydrolipoyl transacetylase component of the pyruvate dehydrogenase complex from Azotobacter vinelandii. A reconsideration.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 2684741
Journal FEMS Microbiol Lett
Year 1989
Volume 51
Pages 267-71
Authors Russell GC, Williamson RA, Guest JR
Title Partial complementation of pyruvate dehydrogenase deficiency by independently expressed lipoyl and catalytic domains of the dihydrolipoamide acetyltransferase component
Related PDB
Related UniProtKB
[7]
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
[8]
Resource
Comments STRUCTURE BY NMR OF 1-85.
Medline ID 92007876
PubMed ID 1915365
Journal Eur J Biochem
Year 1991
Volume 201
Pages 203-9
Authors Dardel F, Laue ED, Perham RN
Title Sequence-specific 1H-NMR assignments and secondary structure of the lipoyl domain of the Bacillus stearothermophilus pyruvate dehydrogenase multienzyme complex
Related PDB
Related UniProtKB P11961
[9]
Resource
Comments
Medline ID
PubMed ID 1676519
Journal Proc R Soc Lond B Biol Sci
Year 1991
Volume 243
Pages 155-60
Authors Russell GC, Guest JR
Title Site-directed mutagenesis of the lipoate acetyltransferase of Escherichia coli.
Related PDB
Related UniProtKB
[10]
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
[11]
Resource
Comments STRUCTURE BY NMR OF 1-85.
Medline ID 93187999
PubMed ID 8445635
Journal J Mol Biol
Year 1993
Volume 229
Pages 1037-48
Authors Dardel F, Davis AL, Laue ED, Perham RN
Title Three-dimensional structure of the lipoyl domain from Bacillus stearothermophilus pyruvate dehydrogenase multienzyme complex
Related PDB 1lab 1lac
Related UniProtKB P11961
[12]
Resource
Comments STRUCTURE BY NMR OF 128-170.
Medline ID 93195938
PubMed ID 8450544
Journal J Mol Biol
Year 1993
Volume 230
Pages 323-41
Authors Kalia YN, Brocklehurst SM, Hipps DS, Appella E, Sakaguchi K, Perham RN
Title The high-resolution structure of the peripheral subunit-binding domain of dihydrolipoamide acetyltransferase from the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus
Related PDB 2pdd
Related UniProtKB P11961
[13]
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
[14]
Resource
Comments
Medline ID
PubMed ID 8206840
Journal J Bacteriol
Year 1994
Volume 176
Pages 3614-30
Authors Kruger N, Oppermann FB, Lorenzl H, Steinbuchel A
Title Biochemical and molecular characterization of the Clostridium magnum acetoin dehydrogenase enzyme system.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8107106
Journal J Mol Biol
Year 1994
Volume 236
Pages 209-16
Authors Wallis NG, Perham RN
Title Structural dependence of post-translational modification and reductive acetylation of the lipoyl domain of the pyruvate dehydrogenase multienzyme complex.
Related PDB
Related UniProtKB
[16]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 128-170.
Medline ID 96398614
PubMed ID 8805537
Journal Structure
Year 1996
Volume 4
Pages 277-86
Authors Mande SS, Sarfaty S, Allen MD, Perham RN, Hol WG
Title Protein-protein interactions in the pyruvate dehydrogenase multienzyme complex
Related PDB 1ebd
Related UniProtKB P11961
[17]
Resource
Comments
Medline ID
PubMed ID 9043123
Journal Microbiology
Year 1997
Volume 143
Pages 457-66
Authors Guest JR, Attwood MM, Machado RS, Matqi KY, Shaw JE, Turner SL
Title Enzymological and physiological consequences of restructuring the lipoyl domain content of the pyruvate dehydrogenase complex of Escherichia coli.
Related PDB
Related UniProtKB
[18]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9990008
Journal Proc Natl Acad Sci U S A
Year 1999
Volume 96
Pages 1240-5
Authors Izard T, Aevarsson A, Allen MD, Westphal AH, Perham RN, de Kok A, Hol WG
Title Principles of quasi-equivalence and Euclidean geometry govern the assembly of cubic and dodecahedral cores of pyruvate dehydrogenase complexes.
Related PDB 1b5s
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 15514159
Journal Science
Year 2004
Volume 306
Pages 872-6
Authors Frank RA, Titman CM, Pratap JV, Luisi BF, Perham RN
Title A molecular switch and proton wire synchronize the active sites in thiamine enzymes.
Related PDB 1w85 1w88
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 15634348
Journal FEBS J
Year 2005
Volume 272
Pages 259-68
Authors Allen MD, Broadhurst RW, Solomon RG, Perham RN
Title Interaction of the E2 and E3 components of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus. Use of a truncated protein domain in NMR spectroscopy.
Related PDB 1w3d
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 16168437
Journal J Mol Biol
Year 2005
Volume 353
Pages 427-46
Authors Ferguson N, Sharpe TD, Schartau PJ, Sato S, Allen MD, Johnson CM, Rutherford TJ, Fersht AR
Title Ultra-fast barrier-limited folding in the peripheral subunit-binding domain family.
Related PDB 1w4e 1w4f 1w4g 1w4h 2btg 2bth
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 16406408
Journal J Mol Biol
Year 2006
Volume 356
Pages 1237-47
Authors Ferguson N, Sharpe TD, Johnson CM, Fersht AR
Title The transition state for folding of a peripheral subunit-binding domain contains robust and ionic-strength dependent characteristics.
Related PDB 1w4e 1w4f 1w4g
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 the N-terminal lipoyl-binding domain, E3-binding domain, and the C-terminal catalytic domain.
This enzyme catalyzes transfer of acetyl group from lypoyllysine of the lipoyl-binding domain to thiol group of CoA.
The catalytic domain of this enzyme is homologous to that of dihydrolipoamide succinyltransferase (E.C. 2.3.1.61; T00223 in EzCatDB). The catalytic residues seem to be conserved between these two enzymes. Thus, the catalytic mechanism must be the same as that of the homologue.

Created Updated
2004-03-19 2009-09-29