DB code: M00035

RLCP classification 3.113.310400.385 : Transfer
CATH domain 3.40.50.720 : Rossmann fold
3.40.50.261 : Rossmann fold Catalytic domain
3.30.470.20 : D-amino Acid Aminotransferase; Chain A, domain 1 Catalytic domain
3.30.1490.20 : Dna Ligase; domain 1 Catalytic domain
3.40.50.261 : Rossmann fold
E.C. 6.2.1.4
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.30.1490.20 : Dna Ligase; domain 1 T00082 M00037 T00107 T00108
3.30.470.20 : D-amino Acid Aminotransferase; Chain A, domain 1 T00082 D00298 M00037 M00051 T00107 T00108
3.40.50.720 : Rossmann fold S00543 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
O19069 Succinyl-CoA ligase [GDP-forming] subunit alpha, mitochondrial
EC 6.2.1.4
Succinyl-CoA synthetase subunit alpha
SCS-alpha
NP_999574.1 (Protein)
NM_214409.2 (DNA/RNA sequence)
PF02629 (CoA_binding)
PF00549 (Ligase_CoA)
[Graphical View]
P53590 Succinyl-CoA ligase [GDP-forming] subunit beta, mitochondrial
EC 6.2.1.4
GTP-specific succinyl-CoA synthetase subunit beta
Succinyl-CoA synthetase beta-G chain
SCS-betaG
PF08442 (ATP-grasp_2)
PF00549 (Ligase_CoA)
[Graphical View]

KEGG enzyme name
succinate---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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
O19069 SUCA_PIG GTP + succinate + CoA = GDP + phosphate + succinyl-CoA. Heterodimer of an alpha and a beta subunit. Mitochondrion (By similarity).
P53590 SUCB2_PIG GTP + succinate + CoA = GDP + phosphate + succinyl-CoA. Heterodimer of an alpha and a beta subunit. Mitochondrion.

KEGG Pathways
Map code Pathways E.C.
MAP00020 Citrate cycle (TCA cycle)
MAP00640 Propanoate metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00044 C00042 C00010 C00035 C00009 C00091
E.C.
Compound GTP Succinate CoA GDP Orthophosphate Succinyl-CoA
Type amide group,amine group,nucleotide carboxyl group amine group,carbohydrate,nucleotide ,peptide/protein,sulfhydryl group amide group,amine group,nucleotide phosphate group/phosphate ion amine group,carbohydrate,carboxyl group,nucleotide ,peptide/protein,sulfide group
ChEBI 15996
15741
15346
17552
26078
15380
PubChem 6830
1110
21952380
6816
87642
8977
1004
22486802
439161
92133
1eucA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1eudA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1eucA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Bound:PO4 Unbound
1eudA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound 1st-intermediate-bound:NEP
1eucB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1eudB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1eucB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1eudB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1eucB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1eudB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [4] & [5]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1eucA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1eudA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1eucA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain THR 164;GLU 217;HIS 259 GLY 163;THR 164
1eudA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain THR 164;GLU 217; NEP 259(phospholylated) GLY 163;THR 164
1eucB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 206;ASP 220(magnesium binding)
1eudB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 206;ASP 220(magnesium binding)
1eucB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 54 GLY 55
1eudB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 54 GLY 55
1eucB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLY 272;ALA 273;GLY 274
1eudB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLY 272;ALA 273;GLY 274

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

References
[1]
Resource
Comments
Medline ID
PubMed ID 3535876
Journal Biochemistry
Year 1986
Volume 25
Pages 5420-5
Authors Wolodko WT, Kay CM, Bridger WA
Title Active enzyme sedimentation, sedimentation velocity, and sedimentation equilibrium studies of succinyl-CoA synthetases of porcine heart and Escherichia coli.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8060491
Journal J Protein Chem
Year 1994
Volume 13
Pages 177-85
Authors Um HD, Klein C
Title Regulatory role of GDP in the phosphoenzyme formation of guanine nucleotide: specific forms of succinyl coenzyme A synthetase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9261120
Journal J Biol Chem
Year 1997
Volume 272
Pages 21151-9
Authors Ryan DG, Lin T, Brownie E, Bridger WA, Wolodko WT
Title Mutually exclusive splicing generates two distinct isoforms of pig heart succinyl-CoA synthetase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9765291
Journal J Biol Chem
Year 1998
Volume 273
Pages 27580-6
Authors Johnson JD, Mehus JG, Tews K, Milavetz BI, Lambeth DO
Title Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10873456
Journal J Mol Biol
Year 2000
Volume 299
Pages 1325-39
Authors Fraser ME, James MN, Bridger WA, Wolodko WT
Title Phosphorylated and dephosphorylated structures of pig heart, GTP-specific succinyl-CoA synthetase.
Related PDB 1euc 1eud
Related UniProtKB

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.

Created Updated
2004-09-22 2009-02-26