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 hide
6.2.1.4
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RECOMMENDED NAME
GeneOntology No.
succinate-CoA ligase (GDP-forming)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
GTP + succinate + CoA = GDP + phosphate + succinyl-CoA
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acid-thiol ligation
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of antibiotics
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Biosynthesis of secondary metabolites
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Citrate cycle (TCA cycle)
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itaconate degradation
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Metabolic pathways
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Microbial metabolism in diverse environments
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Propanoate metabolism
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TCA cycle III (animals)
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SYSTEMATIC NAME
IUBMB Comments
succinate:CoA ligase (GDP-forming)
Itaconate can act instead of succinate, and ITP instead of GTP.
CAS REGISTRY NUMBER
COMMENTARY hide
9014-36-2
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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-
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Manually annotated by BRENDA team
Brevibacterium leucinophagum
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Manually annotated by BRENDA team
Mima polymorpha
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
Pigeon
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
gene scsA
UniProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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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
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
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key role of the enzyme in the Krebs cycle
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + succinate + CoA
ADP + phosphate + succinyl-CoA
show the reaction diagram
GDP + phosphate + succinyl-CoA
GTP + succinate + CoA
show the reaction diagram
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GTP generated by the activation of succinyl-CoA synthetase could promote key functional roles in the mitochondrial metabolism leading to insulin secretion
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?
GTP + 3-sulfinopropionate + CoA
GDP + phosphate + 3-sulfinopropionyl-CoA
show the reaction diagram
GTP + itaconate + CoA
GDP + phosphate + itaconyl-CoA
show the reaction diagram
GTP + succinate + CoA
?
show the reaction diagram
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + succinate + CoA
ADP + phosphate + succinyl-CoA
show the reaction diagram
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r
GDP + phosphate + succinyl-CoA
GTP + succinate + CoA
show the reaction diagram
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GTP generated by the activation of succinyl-CoA synthetase could promote key functional roles in the mitochondrial metabolism leading to insulin secretion
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?
GTP + succinate + CoA
?
show the reaction diagram
GTP + succinate + CoA
GDP + phosphate + succinyl-CoA
show the reaction diagram
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ADP
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the enzyme either ADP/ATP or GDP/GTP, but prefers GDP/GTP
ATP
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the enzyme either ADP/ATP or GDP/GTP, but prefers GDP/GTP
additional information
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nucleotide-binding site, binding structure crystal structure analysis, modling, detailed overview
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ADP
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guanidinium hydrochloride
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inactivation at 0.5 M
NaI
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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
Urea
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the Thermus aquaticus enzyme loses activity at 4-5.5 M urea, but it regains activity with increasing concentrations of urea, reaching 70% of its original activity in 8.5 M urea
valproyl-CoA
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25-50% inhhibition at 1 mM
zinc chloride
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additional information
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no inhibition by valproic acid
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.004 - 0.036
CoA
0.007
GDP
Pigeon
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pH 8.0, 30C
0.009 - 0.036
GTP
2.26
phosphate
Pigeon
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pH 8.0, 30C
0.39 - 0.49
succinate
0.086
succinyl-CoA
Pigeon
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pH 8.0, 30C
additional information
additional information
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kinetic mechanism and thermodynamic parameter values, quasi-steady-state models, evaluation of five different proposed mechanisms, overview. The ordered ter-ter mechanism with dead-end product inhibition of succinate against succinyl-CoA effectively matches kinetic data on pig heart enzyme, thermodynamic-constrained kinetic model
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22.1
Pigeon
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additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
9.1
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.3 - 7.4
Pigeon
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isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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two distinct ATP-specific and GTP-specific succinyl-CoA synthetases
Manually annotated by BRENDA team
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two distinct ATP-specific and GTP-specific succinyl-CoA synthetases
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
24520
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calculated from amino acid sequence
74000
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enzyme pI 6.0, at pI, gel filtration
77000
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enzyme form pI 5.9, at pH 8.0, gel filtration
78000
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enzyme form pI 6.3, at pH 8.0 and at pI, gel filtration
79250
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enzyme form pI 6.0, at pH 8.0, gel filtration
80000
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enzyme form pI 6.4, at pI, gel filtration
82500
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enzyme form pI 6.4, at pH 8.0, gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heterodimer
the enzyme is composed of an alpha subunit, encoded by SUCLG1, and a beta subunit, encoded by either SUCLA2 or SUCLG2. The alpha-subunit forms a heterodimer with either of its beta-subunits, resulting in an ADP-forming succinate-CoA ligase, EC 6.2.1.5, and a GDP-forming succinate-CoA ligase, EC 6.2.1.4, respectively; the enzyme is composed of an alpha subunit, encoded by SUCLG1, and a beta subunit, encoded by either SUCLA2 or SUCLG2. The alpha-subunit forms a heterodimer with either of its beta-subunits, resulting in an ADP-forming succinate-CoA ligase, EC 6.2.1.5, and a GDP-forming succinate-CoA ligase, EC 6.2.1.4, respectively
heterotetramer
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alpha2beta2
additional information
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structure comparisons, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
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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
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
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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
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purified enzyme in complex with GDP-Mn2+, protein in 50 mM KCl, 0.1 mM EDTA, 50 mM Tris-HCl, pH 7.4, X-ray diffraction structure determination and analysis at 2.35 A resolution
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
48
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10 min, about 40% loss of activity
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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Pigeon
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at least 5 peaks of enzyme having isoelectric points of 6.4, 6.2, 6.0, 5.9 and 5.8
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G-Sephadex Coarse column chromatography, hydroxyapatite column chromatography, and Q-Sepharose Fast Flow column chromatography
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p36, i.e. alpha-subunit of succinyl-CoA synthetase
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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
Sephadex G-50 coarse column gel filtration, Q Sepharose FF column chromatography, and Sephacryl S200 SF gel filtration
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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
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beta-subunit
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crystallization of the phosphorylated and of the dephosphorylated enzyme form, refined to 2.1 A resolution
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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
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expressed in Escherichia coli
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gene scsA, DNA and amino acid sequence determination and analysis, quantitative expression analysis in in tachyzoites and in vitro bradyzoites, overview
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
gene SUCLA2, DNA and amino acid sequence determination and analysis, semi quantitative RT-PCR expression analysis
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two mRNA transcripts arise from a single gene and are generated by mutually exclusive splicing
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
denaturing of the enzyme in 6 M guanidinium chloride for 24 h and refolding by rapid dilution (1:20 v:v) into one of three solutions: benign buffer consisting of 50 mM KCl, 60 mM potassium phosphate pH 7.4, arginine buffer containing 0.67 M L-arginine-HCl, 60 mM potassium phosphate, pH 7.4, or arginine buffer containing 0.67 M L-arginine-HCl, 60 mM potassium phosphate, 50 mM Tris-HCl, pH 8.0, kinetics of refolding, overview. Enzyme refolding in arginine buffer, pH 7.4, is temperature-dependent, the rate of refolding follows apparent first-order kinetics. Omission of phosphate from the buffer does not affect the rate. The refolded enzyme form is much less thermostable than the native form
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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
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