DB code: T00223

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. 2.3.1.61
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.40.50.100 : OB fold (Dihydrolipoamide Acetyltransferase, E2P) M00163 M00222 M00145 M00188 M00189 M00190 M00191 M00208
3.30.559.10 : Chloramphenicol Acetyltransferase M00188 M00189 M00190 M00191
4.10.320.10 : Dihydrolipoamide Transferase M00188 M00189 M00190 M00191

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P0AFG6 Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex
E2
EC 2.3.1.61
Dihydrolipoamide succinyltransferase component of 2-oxoglutarate dehydrogenase complex
NP_415255.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_489006.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF00198 (2-oxoacid_dh)
PF00364 (Biotin_lipoyl)
PF02817 (E3_binding)
[Graphical View]
P20708 Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex
E2
EC 2.3.1.61
Dihydrolipoamide succinyltransferase component of 2-oxoglutarate dehydrogenase complex
PF00198 (2-oxoacid_dh)
PF00364 (Biotin_lipoyl)
PF02817 (E3_binding)
[Graphical View]

KEGG enzyme name
dihydrolipoyllysine-residue succinyltransferase
dihydrolipoamide S-succinyltransferase
dihydrolipoamide succinyltransferase
dihydrolipoic transsuccinylase
dihydrolipolyl transsuccinylase
dihydrolipoyl transsuccinylase
lipoate succinyltransferase (Escherichia coli)
lipoic transsuccinylase
lipoyl transsuccinylase
succinyl-CoA:dihydrolipoamide S-succinyltransferase
succinyl-CoA:dihydrolipoate S-succinyltransferase
enzyme-dihydrolipoyllysine:succinyl-CoA S-succinyltransferase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P0AFG6 ODO2_ECOLI Succinyl-CoA + enzyme N(6)- (dihydrolipoyl)lysine = CoA + enzyme N(6)-(S- succinyldihydrolipoyl)lysine. Forms a 24-polypeptide structural core with octahedral symmetry. Binds 1 lipoyl cofactor covalently.
P20708 ODO2_AZOVI Succinyl-CoA + enzyme N(6)- (dihydrolipoyl)lysine = CoA + enzyme N(6)-(S- succinyldihydrolipoyl)lysine. Forms a 24-polypeptide structural core with octahedral symmetry. Binds 1 lipoyl cofactor covalently.

KEGG Pathways
Map code Pathways E.C.
MAP00020 Citrate cycle (TCA cycle)
MAP00310 Lysine degradation

Compound table
Substrates Products Intermediates
KEGG-id C00010 C01169 C00091 C00579
E.C.
Compound CoA S-Succinyldihydrolipoamide Succinyl-CoA Dihydrolipoamide
Type amine group,carbohydrate,nucleotide ,peptide/protein,sulfhydryl group amide group,carbohydrate,carboxyl group,lipid,sulfhydryl group,sulfide group amine group,carbohydrate,carboxyl group,nucleotide ,peptide/protein,sulfide group amide group,lipid,sulfhydryl group
ChEBI 15346
17432
15380
17694
PubChem 6816
87642
11953795
439161
92133
663
1ghjA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1ghkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1pmrA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1balA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1bblA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1w4hA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
2btgA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
2bthA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1c4tA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1c4tB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1c4tC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1e2oA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1sczA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound

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

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ghjA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ghkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1pmrA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1balA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1bblA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1w4hA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2btgA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2bthA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1c4tA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 184;THR 323;HIS 375;ASP 379 HIS 375
1c4tB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 184;THR 323;HIS 375;ASP 379 HIS 375
1c4tC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 184;THR 323;HIS 375;ASP 379 HIS 375
1e2oA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 184;THR 323;HIS 375;ASP 379 HIS 375
1sczA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 184;THR 323;HIS 375;ASP 379 HIS 375

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[9]
p.660-662
[11]
p.41-42

References
[1]
Resource
Comments
Medline ID
PubMed ID 6341609
Journal J Mol Biol
Year 1983
Volume 165
Pages 523-41
Authors Wagenknecht T, Francis N, DeRosier DJ
Title alpha-Ketoglutarate dehydrogenase complex may be heterogeneous in quaternary structure.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 6403946
Journal Proc Natl Acad Sci U S A
Year 1983
Volume 80
Pages 2226-30
Authors Hackert ML, Oliver RM, Reed LJ
Title Evidence for a multiple random coupling mechanism in the alpha-ketoglutarate dehydrogenase multienzyme complex of Escherichia coli: a computer model analysis.
Related PDB
Related UniProtKB
[3]
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 1bal 1bbl
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 6380587
Journal Biochemistry
Year 1984
Volume 23
Pages 3383-9
Authors Wagenknecht T, Frank J
Title Localization of lipoyl-bearing domains in the alpha-ketoglutarate dehydrogenase multienzyme complex.
Related PDB
Related UniProtKB
[5]
Resource
Comments STRUCTURE BY NMR OF 103-152STRUCTURE BY NMR OF 103-152
Medline ID 92207970
PubMed ID 1554728
Journal Biochemistry
Year 1992
Volume 31
Pages 3463-71
Authors Robien MA, Clore GM, Omichinski JG, Perham RN, Appella E, Sakaguchi K, Gronenborn AM
Title Three-dimensional solution structure of the E3-binding domain of the dihydrolipoamide succinyltransferase core from the 2-oxoglutarate dehydrogenase multienzyme complex of Escherichia coli.
Related PDB
Related UniProtKB P0AFG6
[6]
Resource
Comments STRUCTURE BY NMR OF 1-79.
Medline ID 96096733
PubMed ID 8529634
Journal Eur J Biochem
Year 1995
Volume 234
Pages 148-59
Authors Berg A, Smits O, de Kok A, Vervoort J
Title Sequential 1H and 15N nuclear magnetic resonance assignments and secondary structure of the lipoyl domain of the 2-oxoglutarate dehydrogenase complex from Azotobacter vinelandii. Evidence for high structural similarity with the lipoyl domain of the pyruvate dehydrogenase complex.
Related PDB
Related UniProtKB P20708
[7]
Resource
Comments STRUCTURE BY NMR OF 1-77.
Medline ID 96374493
PubMed ID 8780784
Journal J Mol Biol
Year 1996
Volume 261
Pages 432-42
Authors Berg A, Vervoort J, de Kok A
Title Solution structure of the lipoyl domain of the 2-oxoglutarate dehydrogenase complex from Azotobacter vinelandii.
Related PDB 1ghj 1ghk
Related UniProtKB P20708
[8]
Resource
Comments STRUCTURE BY NMR OF 1-80
Medline ID 97107536
PubMed ID 8950276
Journal J Mol Biol
Year 1996
Volume 264
Pages 179-90
Authors Ricaud PM, Howard MJ, Roberts EL, Broadhurst RW, Perham RN
Title Three-dimensional structure of the lipoyl domain from the dihydrolipoyl succinyltransferase component of the 2-oxoglutarate dehydrogenase multienzyme complex of Escherichia coli.
Related PDB 1pmr
Related UniProtKB P0AFG6
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 172-404
Medline ID 98344105
PubMed ID 9677295
Journal J Mol Biol
Year 1998
Volume 280
Pages 655-68
Authors Knapp JE, Mitchell DT, Yazdi MA, Ernst SR, Reed LJ, Hackert ML
Title Crystal structure of the truncated cubic core component of the Escherichia coli 2-oxoglutarate dehydrogenase multienzyme complex.
Related PDB 1e2o
Related UniProtKB P0AFG6
[10]
Resource
Comments
Medline ID
PubMed ID 10806400
Journal Eur J Biochem
Year 2000
Volume 267
Pages 3005-16
Authors Koike K, Suematsu T, Ehara M
Title Cloning, overexpression and mutagenesis of cDNA encoding dihydrolipoamide succinyltransferase component of the porcine 2-oxoglutarate dehydrogenase complex.
Related PDB
Related UniProtKB
[11]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 172-404
Medline ID 20201852
PubMed ID 10739245
Journal Protein Sci
Year 2000
Volume 9
Pages 37-48
Authors Knapp JE, Carroll D, Lawson JE, Ernst SR, Reed LJ, Hackert ML
Title Expression, purification, and structural analysis of the trimeric form of the catalytic domain of the Escherichia coli dihydrolipoamide succinyltransferase.
Related PDB 1c4t
Related UniProtKB P0AFG6
[12]
Resource
Comments
Medline ID
PubMed ID 12481137
Journal Science
Year 2002
Volume 298
Pages 2191-5
Authors Garcia-Mira MM, Sadqi M, Fischer N, Sanchez-Ruiz JM, Munoz V
Title Experimental identification of downhill protein folding.
Related PDB
Related UniProtKB
[13]
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

Comments
PDB structures, 1ghj, 1ghk & 1pmr, correspond to the first domain of this enzyme, lipoyl domain, the other structures, 1bal & 1bbl, comprises the second domain, E3-binding domain, and the rest of structures, 1c4t & 1e2o, are the third domain, catalytic one.
According to the literature [9] & [11], the reaction proceeds as follows:
(1) His375 acts as a general base to abstract a proton from the acceptor group, thiol group of CoA.
(2) Asp379 is thought to modulate the catalytic histidine, His375, by interacting with the residue and Arg184 ([9] & [11]). (Here, the mainchain carbonyl oxygen of His375 might modulate its own sidechain. see M00189 in EzCatDB)
(3) The activated thiolate makes a nucleophilic attack on the transferred group, carbonyl carbon atom of the succinylated substrate, resulting in the formation of a tetrahedral intermediate.
(4) This intermediate is stabilized by the hydroxyl group of Thr323' from the next subunit (3-fold-related subunit).
(5) The breakdown of this intermediate results in the transfer of the succinyl group to CoA and protonation of the dihydrolipoyl group (see [9] & [11]). (His375 can be involved in this protonation.)

Created Updated
2002-12-03 2009-09-29