EzCatDB: M00035
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DB codeM00035
RLCP classification3.113.310400.385 : Transfer
CATH domainDomain 13.40.50.720 : Rossmann fold
Domain 23.40.50.261 : Rossmann foldCatalytic domain
Domain 33.30.470.20 : D-amino Acid Aminotransferase; Chain A, domain 1Catalytic domain
Domain 43.30.1490.20 : Dna Ligase; domain 1Catalytic domain
Domain 53.40.50.261 : Rossmann fold
E.C.6.2.1.4

CATH domainRelated DB codes (homologues)
3.30.1490.20 : Dna Ligase; domain 1T00082,M00037,T00107,T00108
3.30.470.20 : D-amino Acid Aminotransferase; Chain A, domain 1T00082,D00298,M00037,M00051,T00107,T00108
3.40.50.720 : Rossmann foldS00543,S00551,S00552,S00553,S00602,S00604,S00605,S00608,S00610,S00625,S00319,S00328,S00329,S00330,S00331,S00332,D00456,D00457,D00458,S00324,S00320,S00325,S00326,S00327,D00459,S00335,S00336,S00334,T00219,S00339,D00513,D00001,D00002,D00003,D00005,D00007,D00008,D00010,D00012,D00017,D00018,D00023,D00027,D00028,D00031,D00032,D00033,D00034,D00035,D00037,D00048,D00071,D00476,D00481,D00482,D00490,D00492,D00494,D00545,D00601,D00603,D00604,D00605,D00615,D00845,D00857,D00858,M00161,M00171,M00210,T00002,T00010,T00011,T00015,T00227,T00247,T00408,T00414,D00827,D00262,D00274,D00275,T00109

Enzyme Name
UniProtKBKEGG

O19069P53590
Protein nameSuccinyl-CoA ligase [GDP-forming] subunit alpha, mitochondrialSuccinyl-CoA ligase [GDP-forming] subunit beta, mitochondrialsuccinate---CoA ligase (GDP-forming)
succinyl-CoA synthetase (GDP-forming)
succinyl coenzyme A synthetase (guanosine diphosphate-forming)
succinate thiokinase
succinic thiokinase
succinyl coenzyme A synthetase
succinate-phosphorylating enzyme
P-enzyme
SCS
G-STK
succinyl coenzyme A synthetase (GDP-forming)
succinyl CoA synthetase
succinyl coenzyme A synthetase
SynonymsEC 6.2.1.4
Succinyl-CoA synthetase subunit alpha
SCS-alpha
EC 6.2.1.4
GTP-specific succinyl-CoA synthetase subunit beta
Succinyl-CoA synthetase beta-G chain
SCS-betaG
RefSeqNP_999574.1 (Protein)
NM_214409.2 (DNA/RNA sequence)

PfamPF02629 (CoA_binding)
PF00549 (Ligase_CoA)
[Graphical view]
PF08442 (ATP-grasp_2)
PF00549 (Ligase_CoA)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00020Citrate cycle (TCA cycle)
MAP00640Propanoate metabolism

UniProtKB:Accession NumberO19069P53590
Entry nameSUCA_PIGSUCB2_PIG
ActivityGTP + succinate + CoA = GDP + phosphate + succinyl-CoA.GTP + succinate + CoA = GDP + phosphate + succinyl-CoA.
SubunitHeterodimer of an alpha and a beta subunit.Heterodimer of an alpha and a beta subunit.
Subcellular locationMitochondrion (By similarity).Mitochondrion.
Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00044C00042C00010C00035C00009C00091
CompoundGTPSuccinateCoAGDPOrthophosphateSuccinyl-CoA
Typeamide group,amine group,nucleotidecarboxyl groupamine group,carbohydrate,nucleotide,peptide/protein,sulfhydryl groupamide group,amine group,nucleotidephosphate group/phosphate ionamine group,carbohydrate,carboxyl group,nucleotide,peptide/protein,sulfide group
ChEBI15996
15741
15346
17552
26078
15380

PubChem6830
21952380
1110
87642
6816
8977
22486802
1004
92133
439161

               
1eucA01UnboundUnboundUnboundUnboundUnboundUnbound 
1eudA01UnboundUnboundUnboundUnboundUnboundUnbound 
1eucA02UnboundUnboundUnboundUnboundBound:PO4Unbound 
1eudA02UnboundUnboundUnboundUnboundUnboundUnbound1st-intermediate-bound:NEP
1eucB01UnboundUnboundUnboundUnboundUnboundUnbound 
1eudB01UnboundUnboundUnboundUnboundUnboundUnbound 
1eucB02UnboundUnboundUnboundUnboundUnboundUnbound 
1eudB02UnboundUnboundUnboundUnboundUnboundUnbound 
1eucB03UnboundUnboundUnboundUnboundUnboundUnbound 
1eudB03UnboundUnboundUnboundUnboundUnboundUnbound 

Active-site residues
resource
literature [4] & [5]
pdbCatalytic residuesCofactor-binding residuesModified residuesMain-chain involved in catalysis
            
1eucA01 
 
 
 
1eudA01 
 
 
 
1eucA02THR 164;GLU 217;HIS 259
 
                       
GLY 163;THR 164
1eudA02THR 164;GLU 217;       
 
NEP 259(phospholylated)
GLY 163;THR 164
1eucB01 
ASN 206;ASP 220(magnesium binding)
 
 
1eudB01 
ASN 206;ASP 220(magnesium binding)
 
 
1eucB02ARG 54
 
 
GLY 55
1eudB02ARG 54
 
 
GLY 55
1eucB03 
 
 
GLY 272;ALA 273;GLY 274
1eudB03 
 
 
GLY 272;ALA 273;GLY 274


references
[1]
PubMed ID3535876
JournalBiochemistry
Year1986
Volume25
Pages5420-5
AuthorsWolodko WT, Kay CM, Bridger WA
TitleActive enzyme sedimentation, sedimentation velocity, and sedimentation equilibrium studies of succinyl-CoA synthetases of porcine heart and Escherichia coli.
[2]
PubMed ID8060491
JournalJ Protein Chem
Year1994
Volume13
Pages177-85
AuthorsUm HD, Klein C
TitleRegulatory role of GDP in the phosphoenzyme formation of guanine nucleotide: specific forms of succinyl coenzyme A synthetase.
[3]
PubMed ID9261120
JournalJ Biol Chem
Year1997
Volume272
Pages21151-9
AuthorsRyan DG, Lin T, Brownie E, Bridger WA, Wolodko WT
TitleMutually exclusive splicing generates two distinct isoforms of pig heart succinyl-CoA synthetase.
[4]
PubMed ID9765291
JournalJ Biol Chem
Year1998
Volume273
Pages27580-6
AuthorsJohnson JD, Mehus JG, Tews K, Milavetz BI, Lambeth DO
TitleGenetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes.
[5]
CommentsX-ray crystallography
PubMed ID10873456
JournalJ Mol Biol
Year2000
Volume299
Pages1325-39
AuthorsFraser ME, James MN, Bridger WA, Wolodko WT
TitlePhosphorylated and dephosphorylated structures of pig heart, GTP-specific succinyl-CoA synthetase.
Related PDB1euc,1eud

comments
This enzyme catalyzes two transfer reactions, phosphoryl transfer and acyl transfer, according to the literature [5].
The first phosphoryl transfer proceeds as follows:
(1) The interaction of the sidechain of Glu217 (A chain) with that of His259 (A chain) maintains the protonation/charged state of His259 properly, so that His259 can act as a nucleophile.
(2) His259 makes a nucleophilic attack on the gamma-phosphate of the nucleotide (GTP) substrate, resulting in the transient formation of phosphohistidine intermediate. At this reaction, mainchain amide atoms (of Gly163, Thr164 (A chain), Gly55 & residues 272-274 (B chain)) and sidechains of Arg54 (B chain) and Thr164 (A chain) at active site stabilize the transferred phosphate group, whilst magnesium ion may stabilize the leaving alpha- and beta-phosphae of the nucleotide substrate.
(3) The carboxyl oxygen of the second substrate, succinate, may be in-line for a nucleophilic attack on the phoshorylated histidine, releasing the phosphorylated succinate intermediate. Thr164 (A chain) may assist the attacking oxygen atom, by interacting with it.
The second acyl transfer is supposed to be from the phosphorylated intermediate to the sulfur atom of the third substrate, CoA. However, the detailed mechanism has not been elucidated yet.

createdupdated
2004-09-222009-02-26


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