EzCatDB: T00223

DB codeT00223
RLCP classification3.1177.805.87
CATH domainDomain 12.40.50.100
Domain 24.10.320.10
Domain 33.30.559.10Catalytic domain
E.C.2.3.1.61

CATH domainRelated DB codes (homologues)
2.40.50.100M00163,M00222,M00145,M00188,M00189,M00190,M00191,M00208
3.30.559.10M00188,M00189,M00190,M00191
4.10.320.10M00188,M00189,M00190,M00191

Enzyme Name
Swiss-protKEGG

P0AFG6P20708
Protein nameDihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complexDihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complexdihydrolipoyllysine-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
SynonymsE2
EC 2.3.1.61
Dihydrolipoamide succinyltransferase component of 2-oxoglutarate dehydrogenase complex
E2
EC 2.3.1.61
Dihydrolipoamide succinyltransferase component of 2-oxoglutarate dehydrogenase complex

KEGG pathways
MAP codePathways
MAP00020Citrate cycle (TCA cycle)
MAP00310Lysine degradation

Swiss-prot:Accession NumberP0AFG6P20708
Entry nameODO2_ECOLIODO2_AZOVI
ActivitySuccinyl-CoA + enzyme N(6)- (dihydrolipoyl)lysine = CoA + enzyme N(6)-(S- succinyldihydrolipoyl)lysine.Succinyl-CoA + enzyme N(6)- (dihydrolipoyl)lysine = CoA + enzyme N(6)-(S- succinyldihydrolipoyl)lysine.
SubunitForms a 24-polypeptide structural core with octahedral symmetry.Forms a 24-polypeptide structural core with octahedral symmetry.
Subcellular location

CofactorBinds 1 lipoyl cofactor covalently.Binds 1 lipoyl cofactor covalently.


SubstratesProducts
KEGG-idC00010C01169C00091C00579
CompoundCoAS-SuccinyldihydrolipoamideSuccinyl-CoADihydrolipoamide
Typeamine group,carbohydrate,nucleotide,peptide/protein,sulfhydryl groupamide group,carbohydrate,carboxyl group,lipid,sulfhydryl group,sulfide groupamine group,carbohydrate,carboxyl group,nucleotide,peptide/protein,sulfide groupamide group,lipid,sulfhydryl group
1ghjAUnboundUnboundUnboundUnbound
1ghkAUnboundUnboundUnboundUnbound
1pmrAUnboundUnboundUnboundUnbound
1balAUnboundUnboundUnboundUnbound
1bblAUnboundUnboundUnboundUnbound
1w4hAUnboundUnboundUnboundUnbound
2btgAUnboundUnboundUnboundUnbound
2bthAUnboundUnboundUnboundUnbound
1c4tAUnboundUnboundUnboundUnbound
1c4tBUnboundUnboundUnboundUnbound
1c4tCUnboundUnboundUnboundUnbound
1e2oAUnboundUnboundUnboundUnbound
1sczAUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot
pdbCatalytic residuesMain-chain involved in catalysis
1ghjA

1ghkA

1pmrA

1balA

1bblA

1w4hA

2btgA

2bthA

1c4tAARG 184;THR 323;HIS 375;ASP 379
HIS 375
1c4tBARG 184;THR 323;HIS 375;ASP 379
HIS 375
1c4tCARG 184;THR 323;HIS 375;ASP 379
HIS 375
1e2oAARG 184;THR 323;HIS 375;ASP 379
HIS 375
1sczAARG 184;THR 323;HIS 375;ASP 379
HIS 375

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[9]p.660-662
[11]p.41-42

references
[1]
PubMed ID6341609
JournalJ Mol Biol
Year1983
Volume165
Pages523-41
AuthorsWagenknecht T, Francis N, DeRosier DJ
Titlealpha-Ketoglutarate dehydrogenase complex may be heterogeneous in quaternary structure.
[2]
PubMed ID6403946
JournalProc Natl Acad Sci U S A
Year1983
Volume80
Pages2226-30
AuthorsHackert ML, Oliver RM, Reed LJ
TitleEvidence for a multiple random coupling mechanism in the alpha-ketoglutarate dehydrogenase multienzyme complex of Escherichia coli: a computer model analysis.
[3]
PubMed ID6376124
JournalEur J Biochem
Year1984
Volume141
Pages361-74
AuthorsSpencer ME, Darlison MG, Stephens PE, Duckenfield IK, Guest JR
TitleNucleotide sequence of the sucB gene encoding the dihydrolipoamide succinyltransferase of Escherichia coli K12 and homology with the corresponding acetyltransferase.
Related PDB1bal,1bbl
[4]
PubMed ID6380587
JournalBiochemistry
Year1984
Volume23
Pages3383-9
AuthorsWagenknecht T, Frank J
TitleLocalization of lipoyl-bearing domains in the alpha-ketoglutarate dehydrogenase multienzyme complex.
[5]
CommentsSTRUCTURE BY NMR OF 103-152STRUCTURE BY NMR OF 103-152
Medline ID92207970
PubMed ID1554728
JournalBiochemistry
Year1992
Volume31
Pages3463-71
AuthorsRobien MA, Clore GM, Omichinski JG, Perham RN, Appella E, Sakaguchi K, Gronenborn AM
TitleThree-dimensional solution structure of the E3-binding domain of the dihydrolipoamide succinyltransferase core from the 2-oxoglutarate dehydrogenase multienzyme complex of Escherichia coli.
Related Swiss-protP0AFG6
[6]
CommentsSTRUCTURE BY NMR OF 1-79.
Medline ID96096733
PubMed ID8529634
JournalEur J Biochem
Year1995
Volume234
Pages148-59
AuthorsBerg A, Smits O, de Kok A, Vervoort J
TitleSequential 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 Swiss-protP20708
[7]
CommentsSTRUCTURE BY NMR OF 1-77.
Medline ID96374493
PubMed ID8780784
JournalJ Mol Biol
Year1996
Volume261
Pages432-42
AuthorsBerg A, Vervoort J, de Kok A
TitleSolution structure of the lipoyl domain of the 2-oxoglutarate dehydrogenase complex from Azotobacter vinelandii.
Related PDB1ghj,1ghk
Related Swiss-protP20708
[8]
CommentsSTRUCTURE BY NMR OF 1-80
Medline ID97107536
PubMed ID8950276
JournalJ Mol Biol
Year1996
Volume264
Pages179-90
AuthorsRicaud PM, Howard MJ, Roberts EL, Broadhurst RW, Perham RN
TitleThree-dimensional structure of the lipoyl domain from the dihydrolipoyl succinyltransferase component of the 2-oxoglutarate dehydrogenase multienzyme complex of Escherichia coli.
Related PDB1pmr
Related Swiss-protP0AFG6
[9]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 172-404
Medline ID98344105
PubMed ID9677295
JournalJ Mol Biol
Year1998
Volume280
Pages655-68
AuthorsKnapp JE, Mitchell DT, Yazdi MA, Ernst SR, Reed LJ, Hackert ML
TitleCrystal structure of the truncated cubic core component of the Escherichia coli 2-oxoglutarate dehydrogenase multienzyme complex.
Related PDB1e2o
Related Swiss-protP0AFG6
[10]
PubMed ID10806400
JournalEur J Biochem
Year2000
Volume267
Pages3005-16
AuthorsKoike K, Suematsu T, Ehara M
TitleCloning, overexpression and mutagenesis of cDNA encoding dihydrolipoamide succinyltransferase component of the porcine 2-oxoglutarate dehydrogenase complex.
[11]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 172-404
Medline ID20201852
PubMed ID10739245
JournalProtein Sci
Year2000
Volume9
Pages37-48
AuthorsKnapp JE, Carroll D, Lawson JE, Ernst SR, Reed LJ, Hackert ML
TitleExpression, purification, and structural analysis of the trimeric form of the catalytic domain of the Escherichia coli dihydrolipoamide succinyltransferase.
Related PDB1c4t
Related Swiss-protP0AFG6
[12]
PubMed ID12481137
JournalScience
Year2002
Volume298
Pages2191-5
AuthorsGarcia-Mira MM, Sadqi M, Fischer N, Sanchez-Ruiz JM, Munoz V
TitleExperimental identification of downhill protein folding.
[13]
PubMed ID16168437
JournalJ Mol Biol
Year2005
Volume353
Pages427-46
AuthorsFerguson N, Sharpe TD, Schartau PJ, Sato S, Allen MD, Johnson CM, Rutherford TJ, Fersht AR
TitleUltra-fast barrier-limited folding in the peripheral subunit-binding domain family.
Related PDB1w4e,1w4f,1w4g,1w4h,2btg,2bth

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.)

createdupdated
2002-12-032009-09-29
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
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)

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