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Information on EC 2.8.3.18 - succinyl-CoA:acetate CoA-transferase and Organism(s) Acetobacter aceti and UniProt Accession B3EY95
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2.8.3.18 succinyl-CoA:acetate CoA-transferaseIUBMB Comments
In some bacteria the enzyme catalyses the conversion of acetate to acetyl-CoA as part of a modified tricarboxylic acid (TCA) cycle [3,5,6]. In other organisms it converts acetyl-CoA to acetate during fermentation [1,2,4,7]. In some organisms the enzyme also catalyses the activity of EC 2.8.3.27, propanoyl-CoA:succinate CoA transferase.
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Word Map
- 2.8.3.18
- acetyl-coa
- phosphotransacetylase
- adduct
-
trypanosomatids
-
acetate-producing
- brucei
-
anhydride
- thioesters
-
oxyanion
- hydrogenosomes
-
protozoan
-
citric
-
trypanosoma
-
acetobacter
- medicine
The taxonomic range for the selected organisms is: Acetobacter aceti
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Synonyms
succinyl-coa:acetate coa-transferase, tvasct, acetyl:succinate coa-transferase, acetic acid resistance factor, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AarC
-
-
-
-
SCACT
SCACT
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
succinyl-CoA + acetate = acetyl-CoA + succinate
reaction displays ping-pong kinetics and a modified-enzyme mechanism
succinyl-CoA + acetate = acetyl-CoA + succinate
the general half-reaction for class I CoA-transferases shows two tetrahedral oxyanion intermediates, which differ by whether CoA becomes attached to the external carbonyl, provided by the acyl-CoA/carboxylate substrate, or the internal carbonyl, provided by the essential active-site glutamate. Following exchange of the carboxylate product, the second half-reaction proceeds in the reverse order of the first half-reaction. In the first half-reaction, the binary enzyme·acyl-CoA complex is converted into a CoA thiolate complex that also contains an acylglutamyl anhydride adduct. Ping-pong kinetic mechanism. Val270 has a dual influence on carboxylate substrate selectivity, as a gate and as a clamp, Arg228 has an important kinetic role in carboxylate substrate binding. The auxiliary site nonselectively binds carboxylates at the threshold of the catalytic pocket, while selectivity is enforced by the conserved gating residue Val270 and the interior of the catalytic pocke
PATHWAY SOURCE
PATHWAYS
KEGG
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
succinyl-CoA:acetate CoA-transferase
In some bacteria the enzyme catalyses the conversion of acetate to acetyl-CoA as part of a modified tricarboxylic acid (TCA) cycle [3,5,6]. In other organisms it converts acetyl-CoA to acetate during fermentation [1,2,4,7]. In some organisms the enzyme also catalyses the activity of EC 2.8.3.27, propanoyl-CoA:succinate CoA transferase.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + acetoacetate
acetoacetyl-CoA + acetate
0.35% of the activity with succinate
-
-
r
acetyl-CoA + D-malate
D-malyl-CoA + acetate
0.28% of the activity with succinate
-
-
r
acetyl-CoA + fumarate
fumaryl-CoA + acetate
0.20% of the activity with succinate
-
-
r
acetyl-CoA + propionate
propionyl-CoA + acetate
0.34% of the activity with succinate
-
-
r
succinyl-CoA + DL-methylsuccinate
DL-methylsuccinyl-CoA + succinate
-
-
-
?
succinyl-CoA + acetate
acetyl-CoA + succinate
5.1% of the activity with succinate + acetyl-CoA
-
-
r
succinyl-CoA + acetate
acetyl-CoA + succinate
via an acetylglutamyl anhydride intermediate and glutamyl-CoA thioester adduct
-
-
?
additional information
?
-
no activity with glycolate, glyoxylate, oxalate, trifluoroacetate, DL-lactate, L-lactate, malonate, pyruvate, maleate, butyrate, D-tartrate, L-tartrate, 2-oxooglutarate, citrate, or DL-isocitrate
-
-
?
additional information
?
-
-
no activity with glycolate, glyoxylate, oxalate, trifluoroacetate, DL-lactate, L-lactate, malonate, pyruvate, maleate, butyrate, D-tartrate, L-tartrate, 2-oxooglutarate, citrate, or DL-isocitrate
-
-
?
additional information
?
-
substrate specificity, overview. Acetoacetate, propionate, D-malate, fumarate, L-malate, formate, oxaloacetate, DL-methylsuccinate, glutarate are alternate substrates, no activity with glycolate, glyoxylate, oxalate, trifluoroacetate, DL-lactate, L-lactate, malonate, pyruvate, maleate, butyrate, D-tartrate, L-tartrate, 2-oxooglutarate, citrate, or DL-isocitrate
-
-
?
additional information
?
-
-
substrate specificity, overview. Acetoacetate, propionate, D-malate, fumarate, L-malate, formate, oxaloacetate, DL-methylsuccinate, glutarate are alternate substrates, no activity with glycolate, glyoxylate, oxalate, trifluoroacetate, DL-lactate, L-lactate, malonate, pyruvate, maleate, butyrate, D-tartrate, L-tartrate, 2-oxooglutarate, citrate, or DL-isocitrate
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
succinyl-CoA + acetate
acetyl-CoA + succinate
via an acetylglutamyl anhydride intermediate and glutamyl-CoA thioester adduct
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
acetate
substrate inhibition. Enzyme shows an increased substrate inhibition at a lower pH
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
steady-state kinetic analysis using a Michaelis-Menten model, a substrate inhibition model, or a competitive inhibition model, overview. Arg228 has an important kinetic role in carboxylate substrate binding
-
additional information
additional information
-
steady-state kinetic analysis using a Michaelis-Menten model, a substrate inhibition model, or a competitive inhibition model, overview. Arg228 has an important kinetic role in carboxylate substrate binding
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.029
acetate
mutant S71A, pH 8.0, temperature not specified in the publication
0.16
acetate
mutant N347A, pH 8.0, temperature not specified in the publication
0.6
acetate
mutant R228E, pH 8.0, temperature not specified in the publication
3
acetate
mutant E435D, pH 8.0, temperature not specified in the publication
4
acetate
wild-type, pH 8.0, temperature not specified in the publication
0.7
acetyl-CoA
mutant N347A, pH 8.0, temperature not specified in the publication
0.7
acetyl-CoA
mutant S71A, pH 8.0, temperature not specified in the publication
3.4
acetyl-CoA
wild-type, pH 8.0, temperature not specified in the publication
5.2
acetyl-CoA
mutant E435D, pH 8.0, temperature not specified in the publication
0.03
succinate
mutant S71A, pH 8.0, temperature not specified in the publication
0.3
succinate
mutant R228E, pH 8.0, temperature not specified in the publication
2.7
succinate
mutant N347A, pH 8.0, temperature not specified in the publication
73
succinate
mutant E435D, pH 8.0, temperature not specified in the publication
79
succinate
wild-type, pH 8.0, temperature not specified in the publication
0.009
succinyl-CoA
pH 8.0, 30°C, His6-tagged wild-type enzyme and mutant E435D
0.074
succinyl-CoA
mutant S71A, pH 8.0, temperature not specified in the publication
0.13
succinyl-CoA
mutant R228E, pH 8.0, temperature not specified in the publication
0.39
succinyl-CoA
mutant N347A, pH 8.0, temperature not specified in the publication
9
succinyl-CoA
wild-type, pH 8.0, temperature not specified in the publication
9
succinyl-CoA
mutant E435D, pH 8.0, temperature not specified in the publication
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
500
acetate
pH: 5.0, shows an increased substrate inhibition at a lower pH
1100
acetate
pH: 6.0, shows an increased substrate inhibition at a lower pH
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the enzyme belongs to the class I-CoA-transferases, which, typified by mitochondrial succinyl-CoA:3-oxoacid CoA-transferase, form multiple covalent adducts involving an essential glutamate residue. Arg228 is found in only AarC and several closely allied SCACT group sequences, EC 6.2.1
physiological function
additional information
physiological function
enzyme AarC is succinyl-coenzyme A:acetate CoA-transferase, which replaces succinyl-CoA synthetase in a variant citric acid cycle. This bypass appears to reduce metabolic demand for free CoA, reliance upon nucleotide pools, and the likely effect of variable cytoplasmic pH upon citric acid cycle flux
physiological function
the enzyme is an acetic acid resistance factor AarC that is required for acetate resistance by vinegar factory strain Acetobacter aceti 1023. The enzyme acts in a variant citric acid cycle that overoxidizes acetic acid to CO2, which then diffuses into the acidic culture medium
additional information
the nucleophilic glutamate is held at a near-ideal angle for attack as the thioester oxygen is forced into an oxyanion hole composed of Gly388 NH and CoA N2''. CoA is nearly immobile along its entire length during all stages of the enzyme reaction. Spatial and sequence conservation of key residues indicates that this mechanism is general among class I CoA-transferases, structural model for the AarC mechanism, overview. An auxiliary carboxylate binding site, located just outside the AarC catalytic pocket, contributes to the efficient recognition and conversion of the physiological carboxylate substrates. Protein conformational dynamics, overview. Arg228 has an important kinetic role in carboxylate substrate binding. Regulation of carboxylate access to the active-site glutamate, overview
additional information
-
the nucleophilic glutamate is held at a near-ideal angle for attack as the thioester oxygen is forced into an oxyanion hole composed of Gly388 NH and CoA N2''. CoA is nearly immobile along its entire length during all stages of the enzyme reaction. Spatial and sequence conservation of key residues indicates that this mechanism is general among class I CoA-transferases, structural model for the AarC mechanism, overview. An auxiliary carboxylate binding site, located just outside the AarC catalytic pocket, contributes to the efficient recognition and conversion of the physiological carboxylate substrates. Protein conformational dynamics, overview. Arg228 has an important kinetic role in carboxylate substrate binding. Regulation of carboxylate access to the active-site glutamate, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
55847
3 * 55847, ESI-MS, 3 * 55847, calculated, His-tagged recombinant protein
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
trimer
3 * 55847, ESI-MS, 3 * 55847, calculated, His-tagged recombinant protein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structures of a C-terminally His6-tagged form of several wild-type and mutant complexes, including freeze-trapped acetylglutamyl anhydride and glutamyl-CoA thioester adducts. The latter shows the acetate product bound to an auxiliary site that is required for efficient carboxylate substrate recognition. Mutant E294A crystallizes in a closed complex containing dethiaacetyl-CoA, which adopts an unusual curled conformation. A model of the acetyl-CoA Michaelis complex reveals that the nucleophilic glutamate is held at a near-ideal angle for attack as the thioester oxygen is forced into an oxyanion hole composed of Gly388 NH and CoA N2'' CoA is nearly immobile along its entire length during all stages of the enzyme reaction
enzyme bound to dethiaacetyl-CoA and acetate, hanging drop vapor diffusion method, using 0.9 M sodium citrate, 0.1 M imidazole-HCl, pH 8.2, and 25 mM 2-mercaptoethanol
native and C-terminally His6-tagged wild-type enzymes in complexes including freeze-trapped acetylglutamyl anhydride and glutamyl-CoA thioester adducts, hanging drop vapor diffusion method, mixing of 0.002 ml of protein solution containing 5.6 mg/ml AarC in 45 mM potassium phosphate, pH 8.0, 90 mM potassium chloride, and 2 mM CoA or 6.0 mg/ml His6-tagged AarC in 45 mM Tris-HCl, pH 8.0, 90 mM potassium chloride, and 2 mM CoA, with 0.002 ml of reservoir solution containing 0.8-1.0 M sodium citrate, 0.1 M imidazole, pH 8.2, and 25 mM 2-mercaptoethanol for orthorhombic crystals or 1.7-2.0 M ammonium sulfate, 0.2 M sodium chloride, 0.1 M sodium cacodylate, pH 6.5, and 25 mM 2-mercaptoethanol for hexagonal crystals, room temperature of about 22°C, X-ray diffraction structure determination and analysis
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E294A
E435A
E435D
E435Q
N347A
R228E
S71A
E294A
site-directed mutagenesis, the mutant specific catalytic activity is 10000fold reduced compared to the wild-type enzyme, ligand bound crystal structure modeling
E435A
site-directed mutagenesis, the mutant is completely insoluble, ligand bound crystal structure determination and analysis, the mutant crystallizes in a closed complex containing dethiaacetyl-CoA, which adopts an unusual curled conformation
E435D
site-directed mutagenesis, the mutant catalytic properties are nearly equivalent to those of the His6-tagged wild-type enzyme, ligand bound crystal structure modeling
E435Q
site-directed mutagenesis, the mutant is completely insoluble, ligand bound crystal structure modeling
N347A
site-directed mutagenesis, the mutant shows impaired catalytic activity, but the apparent affinities for all four substrates are largely unaffected, ligand bound crystal structure modeling
R228E
site-directed mutagenesis, the mutant has a specific defect in its ability to bind both carboxylate substrates, ligand bound crystal structure modeling
S71A
site-directed mutagenesis, the mutant shows impaired catalytic activity associated with lower kcat values, ligand bound crystal structure modeling
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
using an ammonium sulfate fractionation procedure and an immobilized-metal affinity step. An 8-liter culture yields 9.5 mg of purified protein
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
gene aarC, sequence comparisons and phylogenetic analysis, expression of C-terminally His6-tagged wild-type and mutant enzymes
expressed in Escherichia coli as a C-terminal hexahistidine-containing fusion peptide
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Mullins, E.A.; Francois, J.A.; Kappock, T.J.
A specialized citric acid cycle requiring succinyl-coenzyme A (CoA):acetate CoA-transferase (AarC) confers acetic acid resistance on the acidophile Acetobacter aceti
J. Bacteriol.
190
4933-4940
2008
Acetobacter aceti, Acetobacter aceti (B3EY95)
Mullins, E.A.; Kappock, T.J.
Crystal structures of Acetobacter aceti succinyl-coenzyme A (CoA):acetate CoA-transferase reveal specificity determinants and illustrate the mechanism used by class I CoA-transferases
Biochemistry
51
8422-8434
2012
Acetobacter aceti (B3EY95), Acetobacter aceti, Acetobacter aceti 1023 (B3EY95)
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