Information on EC 6.2.1.4 - succinate-CoA ligase (GDP-forming)

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY
6.2.1.4
-
RECOMMENDED NAME
GeneOntology No.
succinate-CoA ligase (GDP-forming)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
GTP + succinate + CoA = GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Acid-thiol ligation
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
Citrate cycle (TCA cycle)
-
itaconate degradation
-
Metabolic pathways
-
Microbial metabolism in diverse environments
-
Propanoate metabolism
-
TCA cycle VIII (metazoan)
-
SYSTEMATIC NAME
IUBMB Comments
succinate:CoA ligase (GDP-forming)
Itaconate can act instead of succinate, and ITP instead of GTP.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
G-SCS
Pigeon
-
-
G-STK
-
-
-
-
GTP-specific succinyl-CoA synthetase
-
-
SCS
-
-
-
-
SCS
-
-
SCS-alpha
-
-
-
-
SCS-beta
-
-
-
-
SCS-betaG
-
-
-
-
ScsA
Q1KSE5
-
SucCDAm
B3TZD8, B3TZD9
gene name
Succinate thiokinase
-
-
-
-
succinate-CoA ligase
-
-
Succinic thiokinase
-
-
-
-
Succinyl CoA synthetase
-
-
-
-
Succinyl CoA synthetase
-
-
Succinyl coenzyme A synthetase
-
-
-
-
Succinyl coenzyme A synthetase
B3TZD8, B3TZD9
-
Succinyl coenzyme A synthetase (GDP-forming)
-
-
-
-
Succinyl coenzyme A synthetase (guanosine diphosphate-forming)
-
-
-
-
succinyl-CoA synthase
-
-
Succinyl-CoA synthetase
B3TZD8, B3TZD9
-
Succinyl-CoA synthetase
-
-
Succinyl-CoA synthetase
-
-
Succinyl-CoA synthetase
Q1KSE5
-
Succinyl-CoA synthetase (GDP-forming)
-
-
-
-
SUCL
-
-
Synthetase, succinyl coenzyme A (guanosine diphosphate-forming)
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9014-36-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
subunit alpha; i.e. Tetrathiobacter mimigardefordensis, gene SucCDAm
UniProt
Manually annotated by BRENDA team
subunit beta; i.e. Tetrathiobacter mimigardefordensis, gene SucCDAm
UniProt
Manually annotated by BRENDA team
Brevibacterium leucinophagum
-
-
-
Manually annotated by BRENDA team
gene SUCLA2
-
-
Manually annotated by BRENDA team
gene SUCLG1 encodes the alpha-subunit and SUCLG2 encodes the catalytic beta-subunit
-
-
Manually annotated by BRENDA team
Pigeon
-
-
-
Manually annotated by BRENDA team
normal and diabetic
-
-
Manually annotated by BRENDA team
-
Uniprot
Manually annotated by BRENDA team
new-born and adult
-
-
Manually annotated by BRENDA team
gene scsA
UniProt
Manually annotated by BRENDA team
Mima polymorpha
-
-
-
Manually annotated by BRENDA team
additional information
organisms with a succinyl-CoA synthetase with a low Km-value for ADP and a high Km-value for GDP are listed in EC 6.2.1.5
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
-
SUCLG2, EC 6.2.1.5, to a higher degree than SUCLA2, is crucial for mtDNA maintenance involving mitochondrial NDPK
malfunction
-
deficiency of SUCLA2 results in Leigh's or a Leigh-like syndrome with onset of severe hypotonia in early infancy, severemuscular atrophy, and sensorineural hearing impairment. SUCLA2-related mitochondrial DNA depletion syndrome is a result of mutations in the beta subunit of the ADP-dependent isoform of the Krebs cycle succinyl-CoA synthase, phenotype, overview
additional information
-
the GDP-dependent isozyme SUCLG2, EC 6.2.1.5, can complement the SUCLA2-related mitochondrial DNA depletion syndrome
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + succinate + CoA
ADP + phosphate + succinyl-CoA
show the reaction diagram
-
enzyme has a low Km-value for ADP and for GDP
-
-
-
ATP + succinate + CoA
ADP + phosphate + succinyl-CoA
show the reaction diagram
-
enzyme has a very high Km-value for ADP and a low Km-value for GDP
-
-
-
GDP + phosphate + succinyl-CoA
GTP + succinate + CoA
show the reaction diagram
-
GTP generated by the activation of succinyl-CoA synthetase could promote key functional roles in the mitochondrial metabolism leading to insulin secretion
-
?
GTP + 3-sulfinopropionate + CoA
GDP + phosphate + 3-sulfinopropionyl-CoA
show the reaction diagram
-, B3TZD8, B3TZD9
SucCDAm is unspecific regarding ATP or GTP
determination of 3-sulfinopropionyl-CoA structure by using liquid chromatography-electrospray ionization-mass spectrometry
-
?
GTP + itaconate + CoA
GDP + phosphate + itaconyl-CoA
show the reaction diagram
-, B3TZD8, B3TZD9
SucCDAm is unspecific regarding ATP or GTP
-
-
?
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
r
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
?
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
-
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
?
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
?
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
r
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
-
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
O19069
-
-
-
-
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
-
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
?
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
r
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
-
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
-
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
Pigeon
-
-
-
r
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
?
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
Q1KSE5, -
-
-
-
r
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
enzyme has a low Km-value for ADP and for GDP
-
-
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
enzyme has a very high Km-value for ADP and a low Km-value for GDP
-
-
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
succinyl CoA synthetase converts succinyl CoA to succinate in the Krebs cycle. The enzyme activity is reduced, when Helicobacter pylori transforms to the coccoid form, a viable but non-culturable form with reduced metabolic activity, overview
-
-
?
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-, B3TZD8, B3TZD9
SucCDAm is unspecific regarding ATP or GTP
-
-
?
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-, B3TZD8, B3TZD9
succinate is the best substrate, SucCDAm is unspecific regarding ATP or GTP
-
-
?
GTP + succinate + CoA
?
show the reaction diagram
-
recycling of succinate to succinyl-CoA at the expense of GTP, involvement in heme biosynthesis
-
-
-
GTP + succinate + CoA
?
show the reaction diagram
-
not involved in citric acid cycle
-
-
-
GTP + succinate + CoA
?
show the reaction diagram
-
production of succinyl-CoA for ketone body metabolism and as a precursor for porphyrins
-
-
-
additional information
?
-
-
the enzyme supports GTP-dependent anabolic processes
-
-
?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
GDP + phosphate + succinyl-CoA
GTP + succinate + CoA
show the reaction diagram
-
GTP generated by the activation of succinyl-CoA synthetase could promote key functional roles in the mitochondrial metabolism leading to insulin secretion
-
?
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
-
-
-
?
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
Q1KSE5, -
-
-
-
r
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-
succinyl CoA synthetase converts succinyl CoA to succinate in the Krebs cycle. The enzyme activity is reduced, when Helicobacter pylori transforms to the coccoid form, a viable but non-culturable form with reduced metabolic activity, overview
-
-
?
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
-, B3TZD8, B3TZD9
SucCDAm is unspecific regarding ATP or GTP
-
-
?
GTP + succinate + CoA
?
show the reaction diagram
-
recycling of succinate to succinyl-CoA at the expense of GTP, involvement in heme biosynthesis
-
-
-
GTP + succinate + CoA
?
show the reaction diagram
-
not involved in citric acid cycle
-
-
-
GTP + succinate + CoA
?
show the reaction diagram
-
production of succinyl-CoA for ketone body metabolism and as a precursor for porphyrins
-
-
-
additional information
?
-
-
the enzyme supports GTP-dependent anabolic processes
-
-
?
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
GDP
-
allosteric regulator, at high concentration it serves as a substrate. However 100fold lower concentrations of GDP, which do not bind to the catalytic site to induce succinyl-CoA synthetase dephosphorylation, stimulate phosphorylation of p36, the alpha-subunit of succinyl-CoA synthetase
GDP
-
low concentrations stimulate phosphoenzyme formation by either GTP, or succinyl-CoA and phosphate
GTP
-, B3TZD8, B3TZD9
SucCDAm is unspecific regarding ATP or GTP; SucCDAm is unspecific regarding ATP or GTP
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mg2+
-
-
Mg2+
-, B3TZD8, B3TZD9
SucCDAm is Mg2+- or Mn2+-dependent; SucCDAm is Mg2+- or Mn2+-dependent
Mn2+
-
required
Mn2+
-, B3TZD8, B3TZD9
SucCDAm is Mg2+- or Mn2+-dependent; SucCDAm is Mg2+- or Mn2+-dependent
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
NaI
-
41% inhibition at 10 mM, the CoAT activity is inhibited by applying NaI to exponentially growing cell cultures, but the colony-forming ability is not affected
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.004
-
CoA
-
enzyme form pI 6.4
0.005
-
CoA
-
enzyme form pI 5.8
0.006
-
CoA
-
enzyme forms pI 6.2 and pI 6.0
0.007
-
CoA
-
enzyme form pI 5.9
0.036
-
CoA
Pigeon
-
pH 8.0, 30C
0.007
-
GDP
Pigeon
-
pH 8.0, 30C
0.009
-
GTP
-
enzyme form pI 6.4
0.01
-
GTP
-
enzyme form 6.0
0.011
-
GTP
-
enzyme forms pI 6.2, pI 5.9 and pI 5.8
0.014
-
GTP
-
refolded enzyme
0.027
-
GTP
-
native enzyme
0.036
-
GTP
Pigeon
-
pH 8.0, 30C
2.26
-
phosphate
Pigeon
-
pH 8.0, 30C
0.39
-
succinate
-
enzyme form pI 6.4
0.43
-
succinate
-
enzyme forms pI 5.9 and pI 5.8
0.45
-
succinate
-
enzyme form pI 6.0
0.49
-
succinate
Pigeon
-
pH 8.0, 30C
0.086
-
succinyl-CoA
Pigeon
-
pH 8.0, 30C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22.1
-
Pigeon
-
-
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-, B3TZD8, B3TZD9
assay at; assay at
9.1
-
-
assay at
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
-, B3TZD8, B3TZD9
assay at; assay at
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.3
7.4
Pigeon
-
isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
low activity
Manually annotated by BRENDA team
-
newborn and adult
Manually annotated by BRENDA team
-
two distinct ATP-specific and GTP-specific succinyl-CoA synthetases
Manually annotated by BRENDA team
-
two distinct ATP-specific and GTP-specific succinyl-CoA synthetases
Manually annotated by BRENDA team
Pigeon
-
-
Manually annotated by BRENDA team
additional information
Q1KSE5, -
quantitative expression analysis in in tachyzoites and in vitro bradyzoites, overview
Manually annotated by BRENDA team
additional information
-
the enzyme activity is reduced, when Helicobacter pylori transforms to the coccoid form, a viable but non-culturable form with reduced metabolic activity, overview
Manually annotated by BRENDA team
additional information
-
the enzyme is preferably expressed in anabolic tissues
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
24520
-
-
calculated from amino acid sequence
74000
-
-
enzyme pI 6.0, at pI, gel filtration
77000
-
-
enzyme form pI 5.9, at pH 8.0, gel filtration
78000
-
-
enzyme form pI 6.3, at pH 8.0 and at pI, gel filtration
79250
-
-
enzyme form pI 6.0, at pH 8.0, gel filtration
80000
-
-
enzyme form pI 6.4, at pI, gel filtration
82500
-
-
enzyme form pI 6.4, at pH 8.0, gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
Pigeon
-
alphaxbetay, x * 35000 + y * 44500, ATP-specific succinyl-CoA synthetase and GTP-specific succinyl-CoA synthetase incorporate the same alpha-subunit, SDS-PAGE
?
-
precursor of alpha-subunit 31630, calculation from nucleotide sequence
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
the alpha-subunit of succinyl-CoA synthetase undergoes autophosphorylation at a histidine residue. Coprovision of exogenous succinate and CoA results in pronounced dephosphorylation of the phosphorylated alpha-subunit of succinyl-CoA synthetase
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
hanging-drop vapour diffusion method using a precipitant solution containing 10% (v/v) isopropanol, 100 mM ammonium sulfate, 20% (w/v) polyethylene glycol 4000, and 100 mM HEPES or Bicine, pH 7.5
-
hanging drop vapour diffusion method using using 10% polyethylene glycol 3350, 100 mM 4-morpholinoethanesulfonic acid (pH 6.4 for 1 M solution) and 200 mM KCl and a protein solution containing 5 mM GDP and 10 mM MnCl2
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
48
-
-
10 min, about 40% loss of activity
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant soluble enzyme from Escherichia coli strain BL21(DE3)/pLysS by anion exchange chromatography; recombinant soluble enzyme from Escherichia coli strain BL21(DE3)/pLysS by anion exchange chromatography
-, B3TZD8, B3TZD9
p36, i.e. alpha-subunit of succinyl-CoA synthetase
-
-
Pigeon
-
at least 5 peaks of enzyme having isoelectric points of 6.4, 6.2, 6.0, 5.9 and 5.8
-
G-Sephadex Coarse column chromatography, hydroxyapatite column chromatography, and Q-Sepharose Fast Flow column chromatography
-
Sephadex G-50 coarse column gel filtration, Q Sepharose FF column chromatography, and Sephacryl S200 SF gel filtration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
gene sucCD, DNA and amino acid sequence determination and analysis, expression in Escherichia coli strain BL21(DE3)/pLysS; gene sucCD, expression in Escherichia coli strain BL21(DE3)/pLysS
-, B3TZD8, B3TZD9
alpha-subunit, the deduced amino acid sequence shows 75% identity to that of rat liver, which represents a GTP-utilizing form of SCS, and 62% identity to the Escherichia coli protein, which is an ATP-utilizing form
-
gene SUCLA2, DNA and amino acid sequence determination and analysis, semi quantitative RT-PCR expression analysis
-
cytoplasmic precursor of the alpha-subunit, amino acid sequence of the alpha subunit shows an extraordinary degree of homology to the alpha subunbit of Escherichia coli succinyl-CoA synthetase, with more than 70% of the residues identical
-
beta-subunit
-
crystallization of the phosphorylated and of the dephosphorylated enzyme form, refined to 2.1 A resolution
-
expressed in Escherichia coli
-
two mRNA transcripts arise from a single gene and are generated by mutually exclusive splicing
O19069
gene scsA, DNA and amino acid sequence determination and analysis, quantitative expression analysis in in tachyzoites and in vitro bradyzoites, overview
Q1KSE5, -
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-, B3TZD8, B3TZD9
transposon mutagenesis and deletion of gene sucCD, accumulation of 3SP during 3,3'-dithiodipropionic acid degradation occurs in Tn5::mob-induced mutants of Advenella mimigardefordensis strain DPN7T disrupted in sucCD and in the defined deletion mutant Advenella mimigardefordensis DELTAsucCD; transposon mutagenesis and deletion of gene sucCD, accumulation of 3SP during 3,3'-dithiodipropionic acid degradation occurs in Tn5::mob-induced mutants of Advenella mimigardefordensis strain DPN7T disrupted in sucCD and in the defined deletion mutant Advenella mimigardefordensis DELTAsucCD
additional information
-
the severe disorder in patients with SUCLG1 mutations is likely caused by the absence of both ASUCL and G-SUCL, and thereby a compromised formation of both ATP and GTP. Severe lactic acidosis is found in patients with SUCLG1 mutations, phenotype, overview
additional information
-
the GDP-dependent isozyme SUCLG2, EC 6.2.1.5, can complement the SUCLA2-related mitochondrial DNA depletion syndrome, a result of mutations in the beta subunit of the ADP-dependent isoform SUCLA2, EC 6.2.1.4
additional information
Q1KSE5, -
construction of a conditional knock-out mutant for the succinyl-CoA synthetase ScsA, depletion mutant displays a 30% reduction in growth rate, which can be restored by supplementation with 0.002 mM succinate in the tissue culture medium, the mitochondrial membrane potential in these parasites is unaltered, lack of a more severe phenotype, overview
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
refolded from its isolated subunit after denaturation. Refolding of enzyme denatured in 6 M guanidine hydrochloride or of alpha- and beta-subunits isolated in the solvent requires the presence of either ethylene glycol or glycerol, optimally at 20-25% (v/v). MgGTP2- does not stimulate reactivation of the enzyme. Yields of 60% and 40% are obtained in the refolding of denatured enzyme and isolated subunits respectively
-