Information on EC 6.2.1.1 - acetate-CoA ligase

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The expected taxonomic range for this enzyme is: Spermatophyta

EC NUMBER
COMMENTARY
6.2.1.1
-
RECOMMENDED NAME
GeneOntology No.
acetate-CoA ligase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + acetate + CoA = AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
ATP + acetate + CoA = AMP + diphosphate + acetyl-CoA
show the reaction diagram
ordered bi uni uni bi ping-pong mechanism with ordered substrate addition and release
-
ATP + acetate + CoA = AMP + diphosphate + acetyl-CoA
show the reaction diagram
reaction mechanism involving ([Fe4S4]2+ Nip2+ Nid2+) cluster
-
ATP + acetate + CoA = AMP + diphosphate + acetyl-CoA
show the reaction diagram
the ACD reaction follows a four-step mechanism including transient phosphorylation of two active site histidine residues, structure and reaction mechanism of ACD
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Acid-thiol ligation
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
acetate conversion to acetyl-CoA
-
Biosynthesis of secondary metabolites
-
Carbon fixation pathways in prokaryotes
-
chitin degradation to ethanol
-
cis-genanyl-CoA degradation
-
ethanol degradation II
-
ethanol degradation III (oxidative)
-
ethanol degradation IV
-
glutamate degradation VII (to butanoate)
-
Glycolysis / Gluconeogenesis
-
Metabolic pathways
-
Methane metabolism
-
Microbial metabolism in diverse environments
-
Propanoate metabolism
-
Pyruvate metabolism
-
SYSTEMATIC NAME
IUBMB Comments
acetate:CoA ligase (AMP-forming)
Also acts on propanoate and propenoate.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
ACAS
-
-
AceCS
-
-
-
-
AceCS1
-
-
AceCS1
-
liver enzyme, 45.8% amino acid identity between AceCS1 and AceCS2
AceCS2
Q9NUB1
-
AceCS2
-
-
AceCS2
Q99NB1
heart enzyme, 45.8% amino acid identity between AceCS1 and AceCS2
Acetate thiokinase
-
-
-
-
Acetate--CoA ligase
-
-
-
-
acetate:CoA ligase (AMP-forming)
-
-
acetate:CoA ligase (AMP-forming)
Q2XNL6
-
Acetic thiokinase
-
-
-
-
Acetyl activating enzyme
-
-
-
-
Acetyl CoA ligase
-
-
-
-
Acetyl CoA synthase
-
-
-
-
acetyl coenzyme A synthase/carbon monoxide dehydrogenase
-
-
Acetyl coenzyme A synthetase
-
-
-
-
Acetyl coenzyme A synthetase
-
-
Acetyl coenzyme A synthetase
Aliivibrio fischeri ES114
-
-
-
Acetyl coenzyme A synthetase
-
-
Acetyl-CoA synthase
-
-
-
-
Acetyl-CoA synthase
-
-
Acetyl-CoA synthetase
-
-
-
-
Acetyl-CoA synthetase
-
-
Acetyl-CoA synthetase
Aliivibrio fischeri ES114
-
-
-
Acetyl-CoA synthetase
Q9LTG4
-
Acetyl-CoA synthetase
-
-
Acetyl-CoA synthetase
-
-
Acetyl-CoA synthetase
-
-
acetyl-CoA synthetase 2
-
-
Acetyl-coenzyme A synthase
-
-
-
-
Acetyl-coenzyme A synthase
-
-
acetyl-coenzyme A synthase/carbon monoxide dehydrogenase
-
-
acetyl-coenzyme A synthetase
Q9LTG4
-
acetyl-coenzyme A synthetase
-
-
ACS
-
-
-
-
ACS
Q9NR19
-
Acyl-activating enzyme
-
-
-
-
adenosine monophosphate-forming acetyl-CoA synthetase
-
-
adenosine monophosphate-forming acetyl-CoA synthetase
Q2XNL6
-
ADP-forming acetyl-CoA synthetase
-
-
AMP-forming acetyl-CoA synthetase
-
-
AMP-forming acetyl-CoA synthetase
-
-
AMP-forming acetyl-CoA synthetase
Q2XNL6
-
carbon monoxide dehydrogenase/acety-coenzyme A synthase
-
bifunctional enzyme
carbon monoxide dehydrogenase/acetyl-CoA synthase
-
-
MT-ACS1
Methanothermobacter thermautotrophicus Z245
-
-
-
Short chain fatty acyl-CoA synthetase
-
-
-
-
Short-chain acyl-coenzyme A synthetase
-
-
-
-
Synthetase, acetyl coenzyme A
-
-
-
-
CODH/ACS
-
bifunctional enzyme
additional information
-
acetyl-CoA synthase is a subunit of the bifunctional CO dehydrogenase/acetyl-CoA synthase, CODH/ACS, complex
additional information
-
ACD belongs to the protein superfamily of nucleoside diphosphate-forming acyl-CoA synthetases
additional information
-
acetyl-CoA synthetase belongs to the superfamily of adenylate-forming enzymes, whose three-dimensional structures are analogous to one another
additional information
-
Acs is a member of the broadly distributed AMP-forming acyl-CoA synthetase family of enzymes
CAS REGISTRY NUMBER
COMMENTARY
9012-31-1
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
strain ATCC 8554
-
-
Manually annotated by BRENDA team
strain ES114, gene acs
-
-
Manually annotated by BRENDA team
Aliivibrio fischeri ES114
strain ES114, gene acs
-
-
Manually annotated by BRENDA team
Amaranthus sp.
-
-
-
Manually annotated by BRENDA team
gene acs1
Q9LTG4
UniProt
Manually annotated by BRENDA team
gene acsA
-
-
Manually annotated by BRENDA team
-
Swissprot
Manually annotated by BRENDA team
several strains, overview
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
acetyl-coenzyme A synthetase 2-like, mitochondrial. Precursor
SwissProt
Manually annotated by BRENDA team
patients with hepatocellular carcinoma
-
-
Manually annotated by BRENDA team
specific activity of the enzyme is high in cells grown with limited H2 and CO2 supply. It is low in exponentially grown cells
-
-
Manually annotated by BRENDA team
Methanothermobacter thermautotrophicus Z245
strain Z245
-
-
Manually annotated by BRENDA team
formerly Clostridium thermoaceticum strain ATCC 39073
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
pea
-
-
Manually annotated by BRENDA team
strain U
Uniprot
Manually annotated by BRENDA team
genes acdIa and acdIb encoding the alpha and beta subunits
-
-
Manually annotated by BRENDA team
Roseovarius sp.
strain 217
-
-
Manually annotated by BRENDA team
strain 217
-
-
Manually annotated by BRENDA team
2 enzyme forms Acs1p and Acs2p. Under anaerobic glucose-limited conditions only the ACS2 gene is expressed. During carbon-limited growth on glucose, ethanol, and acetate under aerobic conditions both the ACS1 gene and the ACS2 gene are expressed
-
-
Manually annotated by BRENDA team
different isoenzymes are elaborated under aerobic and nonaerobic conditions
-
-
Manually annotated by BRENDA team
different isoenzymes are elaborated under aerobic and nonaerobic conditions; strain LK2G12
-
-
Manually annotated by BRENDA team
strain LK2G12
-
-
Manually annotated by BRENDA team
strain LK2G12; two immunologically distinct enzyme forms are elaborated under aerobic and under nonaerobic conditions
-
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae LK2G12
strain LK2G12
-
-
Manually annotated by BRENDA team
gene acs, different strains
-
-
Manually annotated by BRENDA team
Taxus sp.
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
evolution
-
the metalloprotein acetyl-coenzyme A synthase/carbon monoxide dehydrogenase, ACS/CODH, is a bifunctional metalloenzyme found in anaerobic archaea and bacteria that grow hemoautotrophically on CO or CO2, and is significant for biological carbon fixation and understanding the origin of life
malfunction
-
growth on 10 mM acetate causes an acs+ induction in a Salmonella enterica strain, that cannot acetylate, i.e. inactivate Acs, leads to growth arrest, a condition that correlates with a drop in energy charge in the acetylation-deficient strain, relative to the energy charge in the acetylation-proficient strain. Acs-dependent depletion of ATP, coupled with the rise in AMP levels, prevents the synthesis of ADP needed to replenish the pool of ATP
malfunction
-
deletion of individual and multiple subunits of acetyl-CoA synthetase decreases CoA release activity for several different CoA ester substrates. Deletion of acetyl-CoA synthetases I and II increases production of 3-hydroxypropionate by the metabolically-engineered hyperthermophile Pyrococcus furiosus (containing three enzymes from the CO2 fixation cycle of the thermoacidophilic archaeon Metallosphaerasedula)
metabolism
-
acetyl-CoA synthase, a subunit of the bifunctional CO dehydrogenase/acetyl-CoA synthase, CODH/ACS, complex of Moorella thermoacetica requires reductive activation in order to catalyze acetyl-CoA synthesis and related partial reactions, including the CO/acetyl-CoA exchange reaction. Ferredoxin(II), which harbors two [4Fe-4S] clusters and is an electron acceptor for CODH, serves as a redox activator of ACS. Ferredoxin interfaces with an internal redox shuttle in acetyl-CoA synthase during reductive activation and catalysis. The midpoint reduction potential for the catalytic one-electron redoxactive species in the CO/acetyl-CoAexchange reaction is -511 mV. Incubation of ACS with Fd-II and CO leads to the formation of the NiFeC species. Mechanism, overview
physiological function
-
tumor cells express higher levels of cytosolic acetyl-CoA synthetase ACSS2 under hypoxia than normoxia. Knockdown of ACSS2 by RNA interference in tumor cells enhances tumor cell death under long-term hypoxia in vitro. The ACSS2 suppression slows tumor growth in vivo. Tumor cells excrete acetate and the quantity increases under hypoxia, the pattern of acetate excretion follows the expression pattern of ACSS2. The ACSS2 knockdown leads to a corresponding reduction in the acetate excretion in tumor cells
physiological function
-
an acs2 deletion strain has a reduced replicative life span compared to wild-type and isoform acs1 deletion strains. Replicatively aged acs2 deletion cells contain elevated levels of extrachromosomal rDNA circles, and silencing at the rDNA locus is impaired in an acs2 deletion strain
physiological function
-
acetyl-coenzyme A synthetase activates acetate into acetyl-coenzyme A in most cells. Salmonella enterica requires Acs activity for growth on acetate. The sirtuin-dependent protein acylation/deacylation system, SDPADS, controls the activity of Acs
metabolism
-
activation of weak organic acids by acyl-CoA synthetases is costly to cells, since it requires 2 mol of ATP per mol of substrate; 1 mol of ATP is consumed to activate the organic acid, while the second mol of ATP is needed to convert AMP to ADP, the immediate precursor of ATP. Further loss of energy resources during the course of the Acs reaction is caused by the hydrolysis of diphosphate to monophosphate through pyrophosphate phosphohydrolase, EC 3.6.1.1
additional information
-
growth arrest is caused by elevated Acs activity, while overproduction of ADP-forming Ac-CoA synthesizing systems, EC 6.2.1.13, do not affect the growth behaviour of acetylation-deficient or acetylation-proficient strains, effects of Acs on growth of different strains, also sirtuin-dependent protein acylation/deacylation system-defective strains, overview. Increased CoA biosynthesis partially alleviates the negative effect caused by high Acs activity, regulation, overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
37% of the activity relative to ATP
-
-
-
ADP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
20% of the activity relative to ATP
-
-
-
ADP + phosphate + acetyl-CoA
ATP + acetate + CoA
show the reaction diagram
-
-
-
-
?
ATP + 3-bromopropanoate + CoA
AMP + diphosphate + 3-bromopropanoyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + 3-chloropropanoate + CoA
AMP + diphosphate + 3-chloropropanoyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + 3-methylvalerate + CoA
AMP + diphosphate + 3-methylvaleryl-CoA
show the reaction diagram
-
mutant enzyme W416G catalyzes the reaction, no activity with wild-type enzyme
-
-
?
ATP + 4-methylvalerate + CoA
AMP + diphosphate + 4-methylvaleryl-CoA
show the reaction diagram
-
mutant enzyme W416G catalyzes the reaction, no activity with wild-type enzyme
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
r
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
Amaranthus sp., Zea mays
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-, Q6EMJ3
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
r
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
Q9NR19
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
Q9LTG4
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
highly specific for ATP
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
specific for acetate, no activity with other short-chain fatty acids
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
neither glutathione nor pantetheine can substitute for CoA as acyl acceptor
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
enzyme is involved in pathway of acetate activation. Cells induce acs transcription, and thus the ability to assimilate acetate, in response to rising cAMP levels, falling oxygen partial pressure, and the flux of carbon through pathways associated with acetate metabolism
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
lipogenic enzyme, gene is highly induced by SREBP-1a, SREBP-1c and SREBP-2. The enzyme might also play an important role in basic cellular energy metabolism
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
no relationship between the enzyme level and the capacity of the plants to incorporate CO2 into labeled fatty acids. Very limited role of the enzyme in the biosynthesis of lipids
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
Q9NR19
the enzyme activates acetate so that it can be used for lipid synthesis or for energy generation. The acetyl-CoA synthetase mRNA, and hence the ability of cells to activate acetate, is regulated by sterol regulatory element-binding proteins in parallel with fatty acid synthesis in animal cells
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
the bifunctional enzyme carbon monoxide dehydrogenase/acetyl-coenzyme A synthase is a key enzyme in the Wood-Ljungdahl pathway of carbon fixation, proposed mechanism of the bifunctional enzyme carbon monoxide dehydrogenase/acetyl-coenzyme A synthase
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
Q9NUB1
AceCS2 is reversibly acetylated at Lys642 in the active site of the enzyme. A mammalian sirtuin directly controls the activity of a metabolic enzyme by means of reversible lysine acetylation
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
acetate-CoA ligase is a key enzyme for conversion of acetate to acetyl-CoA
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
Q2XNL6
acetate-CoA ligase is a key enzyme for conversion of acetate to acetyl-CoA
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-, Q6EMJ3
acetyl-CoA synthetase from Pseudomonas putida U is the only acyl-CoA activating enzyme induced by acetate in this bacterium
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
AF-ACS2 has 2.3fold higher affinity and catalytic efficiency with acetate than with propionate. Enzyme shows a strong preference for ATP versus CTP, GTP, TTP, UTP, ITP or ADP, for which less than 5% activity is observed
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-, Q2XNL6
MT-ACS1 is limited to acetate and propionate as acyl substrates. MT-ACS1 has nearly 11fold higher affinity and 14fold higher catalytic efficiency with acetate than with propionate. Enzyme shows a strong preference for ATP versus CTP, GTP, TTP, UTP, ITP or ADP, for which less than 5% activity is observed
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
gene acs encoding the enzyme is regulated by quorum sensing, and acs regulation plays a role in symbiosis, overview
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
formation of enzyme-bound acetyl phosphate and enzyme phosphorylation at His257alpha, respectively. The phosphoryl group is transferred from the His257alpha to ADP via transient phosphorylation of a second conserved histidine residue in the beta-subunit, His71beta
-
-
ir
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
the ACS reaction is catalyzed at the alpha-subunit A-cluster, an [Fe4S4] cubane bridged to a dinickel [NipNid] subcomponent, overview
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
reaction of acetylated ACS with CoA and Fd-II, a step of the catalytic cycle in which the acetylated ACS reacts with CoA to form acetyl-CoA
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
Aliivibrio fischeri ES114
-
-, gene acs encoding the enzyme is regulated by quorum sensing, and acs regulation plays a role in symbiosis, overview
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
Saccharomyces cerevisiae LK2G12
-
-
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
Methanothermobacter thermautotrophicus Z245
-
-
-
-
?
ATP + acetate + CoA
?
show the reaction diagram
-
enzyme form Acs1p is primarily responsible for acetate activation during gluconeogenic growth. Enzyme form Acs2p is likely to be the major producer of cytosolic acetyl-CoA
-
-
-
ATP + acetate + CoA
?
show the reaction diagram
-
enzyme plays an important role in the oxidative part of the aceticlastic reaction
-
-
-
ATP + acetate + seleno-CoA
AMP + diphosphate + acetyl-seleno-CoA
show the reaction diagram
-
-
-
-
-
ATP + acrylate + CoA
AMP + diphosphate + acryloyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acrylate + CoA
AMP + diphosphate + acryloyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acrylate + CoA
AMP + diphosphate + acryloyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + acrylate + CoA
AMP + diphosphate + acryloyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + butyrate + CoA
AMP + diphosphate + butyryl-CoA
show the reaction diagram
-
-
-
-
ATP + butyrate + CoA
AMP + diphosphate + butyryl-CoA
show the reaction diagram
-
no activity
-
-
-
ATP + butyrate + CoA
AMP + diphosphate + butyryl-CoA
show the reaction diagram
-
20% of the activity relative to acetate
-
-
-
ATP + butyrate + CoA
AMP + diphosphate + butyryl-CoA
show the reaction diagram
-
isobutyrate
-
-
-
ATP + butyrate + CoA
AMP + diphosphate + butyryl-CoA
show the reaction diagram
-
25% of the activity with acetate
-
-
?
ATP + butyrate + CoA
AMP + diphosphate + butyryl-CoA
show the reaction diagram
-, Q6EMJ3
26% of the activity with acetyl-CoA
-
-
?
ATP + butyrate + CoA
AMP + diphosphate + butyryl-CoA
show the reaction diagram
-
AF-ACS2
-
-
?
ATP + butyrate + CoA
AMP + diphosphate + butyryl-CoA
show the reaction diagram
Methanothermobacter thermautotrophicus, Methanothermobacter thermautotrophicus Z245
-
mutant enzymes I312A and W416G catalyzes the reaction, no activity with wild-type enzyme
-
-
?
ATP + fluoroacetate + CoA
AMP + diphosphate + fluoroacetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + fluoroacetate + CoA
AMP + diphosphate + fluoroacetyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + formate + CoA
AMP + diphosphate + formyl-CoA
show the reaction diagram
-
27% of the activity with acetate
-
-
?
ATP + heptanoate + CoA
AMP + diphosphate + heptanoyl-CoA
show the reaction diagram
Methanothermobacter thermautotrophicus, Methanothermobacter thermautotrophicus Z245
-
mutant enzyme W416G catalyzes the reaction, no activity with wild-type enzyme
-
-
?
ATP + hexanoate + CoA
AMP + diphosphate + hexanoyl-CoA
show the reaction diagram
Methanothermobacter thermautotrophicus, Methanothermobacter thermautotrophicus Z245
-
mutant enzyme W416G catalyzes the reaction, no activity with wild-type enzyme
-
-
?
ATP + isobutyrate + CoA
AMP + diphosphate + isobutyryl-CoA
show the reaction diagram
-
28% of the activity with acetate
-
-
?
ATP + methacrylic acid + CoA
AMP + diphosphate + methacryloyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + octanoate + CoA
AMP + diphosphate + octanoyl-CoA
show the reaction diagram
-
mutant enzyme W416G catalyzes the reaction, no activity with wild-type enzyme
-
-
?
ATP + pentanoate + CoA
AMP + diphosphate + pentanoyl-CoA
show the reaction diagram
-
6.7% of the activity relative to acetate
-
-
-
ATP + propanoate + CoA
AMP + diphosphate + propanoyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + propanoate + CoA
AMP + diphosphate + propanoyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + propanoate + CoA
AMP + diphosphate + propanoyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + propanoate + CoA
AMP + diphosphate + propanoyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + propanoate + CoA
AMP + diphosphate + propanoyl-CoA
show the reaction diagram
-
-
-
-
-
ATP + propanoate + CoA
AMP + diphosphate + propanoyl-CoA
show the reaction diagram
-
48% of the activity relative to acetate
-
-
-
ATP + propanoate + CoA
AMP + diphosphate + propanoyl-CoA
show the reaction diagram
-
very poor activity
-
-
-
ATP + propanoate + CoA
AMP + diphosphate + propanoyl-CoA
show the reaction diagram
-
5% of the activity relative to acetate
-
-
-
ATP + propanoate + CoA
AMP + diphosphate + propanoyl-CoA
show the reaction diagram
-
118% of the activity with acetate
-
-
?
ATP + propanoate + CoA
AMP + diphosphate + propanoyl-CoA
show the reaction diagram
-
30% of the activity with acetate
-
-
?
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
-
-
-
-
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
-
-
-
-
?
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
Roseovarius sp.
-
aerobic taurine dissimilation via acetate kinase and acetate-CoA ligase. Acetate-CoA ligase operates at the end of the pathway
-
-
?
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
-
nucleocytosolic acetyl-coenzyme a synthetase is required for histone acetylation and global transcription. Acs2p is the major acetyl-CoA source for HATs in glucose
-
-
?
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
-, Q6EMJ3
55% of the activity with acetyl-CoA
-
-
?
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
-
AF-ACS2 has 2.3fold higher affinity and catalytic efficiency with acetate than with propionate. Enzyme shows a strong preference for ATP versus CTP, GTP, TTP, UTP, ITP or ADP, for which less than 5% activity is observed
-
-
?
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
-, Q2XNL6
MT-ACS1 is limited to acetate and propionate as acyl substrates. MT-ACS1 has nearly 11fold higher affinity and 14fold higher catalytic efficiency with acetate than with propionate. Enzyme shows a strong preference for ATP versus CTP, GTP, TTP, UTP, ITP or ADP, for which less than 5% activity is observed
-
-
?
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
-
aerobic taurine dissimilation via acetate kinase and acetate-CoA ligase. Acetate-CoA ligase operates at the end of the pathway
-
-
?
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
Methanothermobacter thermautotrophicus Z245
-
-
-
-
?
ATP + tetrapolyphosphate
adenosine 5'-pentaphosphate
show the reaction diagram
-
-
-
-
ATP + tripolyphosphate
adenosine 5'-tetraphosphate
show the reaction diagram
-
-
-
-
ATP + valerate + CoA
AMP + diphosphate + valeryl-CoA
show the reaction diagram
-, Q6EMJ3
8% of the activity with acetyl-CoA
-
-
?
ATP + valerate + CoA
AMP + diphosphate + valeryl-CoA
show the reaction diagram
-
mutant enzyme W416G catalyzes the reaction, no activity with wild-type enzyme
-
-
?
CheY + acetyl-CoA + ATP
acetyl-CheY + CoA + AMP + diphosphate
show the reaction diagram
-
CheY is the the excitatory response regulator in the chemotaxis system of Escherichia coli, acetyl-CoA synthetase-catalyzed transfer of acetyl groups from acetate to CheY and autocatalyzed transfer from AcCoA, mechanism, overview
-
-
?
CTP + acetate + CoA
CMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
dATP + acetate + CoA
dAMP + diphosphate + acetyl-CoA
show the reaction diagram
Q99NB1
-
-
?
dATP + acetate + CoA
dAMP + diphosphate + acetyl-CoA
show the reaction diagram
-
30% of the activity relative to ATP
-
-
-
dATP + acetate + CoA
dAMP + diphosphate + acetyl-CoA
show the reaction diagram
-
70% of the activity relative to ATP
-
-
dATP + acetate + CoA
dAMP + diphosphate + acetyl-CoA
show the reaction diagram
Q99NB1
AceCS2 plays a role in the production of energy under ketogenic conditions, such as starvation and diabetes. Acetyl-CoAs produced by AceCS2 are utilized mainly for oxidation
-
?
UTP + acetate + CoA
UMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
GTP + acetate + CoA
GMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
enzyme catalyzes propanoate-dependent ATP-diphosphate exchange, reaction mechanism of ATP-diphosphate exchange is ordered, ATP is the first substrate to react with the enzyme, and some form of diphosphate is the first product released
-
-
-
additional information
?
-
-
the enzyme can activate many other molecules to acyl-CoA derivatives: hexanoate, 3-hexenoate, heptanoate, octanoate, 3-octenoate, phenylacetate, 2-thiophene acetate, 3-thiophene acetate
-
-
-
additional information
?
-
-
3'-dephospho-CoASH analogues with a phosphodiester bond are not capable of accepting acetate
-
-
-
additional information
?
-
-
enzyme catalyzes acetate-dependent ATP-diphosphate exchange
-
-
-
additional information
?
-
-
enzyme catalyzes acetate-dependent ATP-diphosphate exchange
-
-
-
additional information
?
-
-
may contribute to the adenosine 5'-tetraphosphate synthesis and adenosine 5'-pentaphosphate synthesis during yeast sporulation
-
-
-
additional information
?
-
-
the enzyme can catalyze the activation to their CoA thioesters of some of the side-chain precursors required in Penicillium chrysogenum and Aspergillus nidulans for the production of several penicillins
-
-
-
additional information
?
-
-
acetate thiokinase is not involved in autotrophic CO2 fixation
-
-
-
additional information
?
-
-
CODH/ACS is a bifunctional enzyme that is responsible for the reduction of CO2 to CO and subsequent assembly of acetyl-CoA, as part of the Wood-Ljungdahl carbon fixation pathway, the enzyme is a key player in the global carbon cycle
-
-
-
additional information
?
-
-
metabolic connection between acetate utilization and cell density
-
-
-
additional information
?
-
Q9LTG4
role of ACS in destroying fermentative intermediates
-
-
-
additional information
?
-
-
the acetyltransferase enzyme, AcuA, controls the activity of the acetyl coenzyme A synthetase, AcsA, by acetylating residue Lys549, overview
-
-
-
additional information
?
-
-
bifunctional Ni-Fe-S containing ACS/CODH, although alpha and beta subunits catalyze separate reactions, they interact functionally when CO2 is used as a substrate in the synthesis of acetyl-CoA
-
-
-
additional information
?
-
-
the enzyme also forms a carbon-nitrogen bond, reaction of EC 6.3.1 acid-ammonia (or amide) ligase, i.e. amide synthase, and EC 6.3.2 acid-amino acid ligase, i.e. peptide synthase, comprising the amino group of the cysteine and the carboxyl group of the acid, overview
-
-
-
additional information
?
-
-
the enzyme is a bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase, Moorella thermoacetica CODH/ACS contains a very long enzyme channel to allow for intermolecular CO transport, mechanism and reaction steps, overview. Structure-function analysis in comparison to monofunctional Acs, overview
-
-
-
additional information
?
-
-
the enzyme performs arsenolysis, the alpha-subunit alone also catalyzes arsenolysis, overview
-
-
-
additional information
?
-
Aliivibrio fischeri ES114
-
metabolic connection between acetate utilization and cell density
-
-
-
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
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
Q9LTG4
-
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
enzyme is involved in pathway of acetate activation. Cells induce acs transcription, and thus the ability to assimilate acetate, in response to rising cAMP levels, falling oxygen partial pressure, and the flux of carbon through pathways associated with acetate metabolism
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
lipogenic enzyme, gene is highly induced by SREBP-1a, SREBP-1c and SREBP-2. The enzyme might also play an important role in basic cellular energy metabolism
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
no relationship between the enzyme level and the capacity of the plants to incorporate CO2 into labeled fatty acids. Very limited role of the enzyme in the biosynthesis of lipids
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
Q9NR19
the enzyme activates acetate so that it can be used for lipid synthesis or for energy generation. The acetyl-CoA synthetase mRNA, and hence the ability of cells to activate acetate, is regulated by sterol regulatory element-binding proteins in parallel with fatty acid synthesis in animal cells
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
the bifunctional enzyme carbon monoxide dehydrogenase/acetyl-coenzyme A synthase is a key enzyme in the Wood-Ljungdahl pathway of carbon fixation
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
Q9NUB1
AceCS2 is reversibly acetylated at Lys642 in the active site of the enzyme. A mammalian sirtuin directly controls the activity of a metabolic enzyme by means of reversible lysine acetylation
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
acetate-CoA ligase is a key enzyme for conversion of acetate to acetyl-CoA
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
Q2XNL6
acetate-CoA ligase is a key enzyme for conversion of acetate to acetyl-CoA
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-, Q6EMJ3
acetyl-CoA synthetase from Pseudomonas putida U is the only acyl-CoA activating enzyme induced by acetate in this bacterium
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
gene acs encoding the enzyme is regulated by quorum sensing, and acs regulation plays a role in symbiosis, overview
-
-
?
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
-
reaction of acetylated ACS with CoA and Fd-II, a step of the catalytic cycle in which the acetylated ACS reacts with CoA to form acetyl-CoA
-
-
?
ATP + acetate + CoA
?
show the reaction diagram
-
enzyme form Acs1p is primarily responsible for acetate activation during gluconeogenic growth. Enzyme form Acs2p is likely to be the major producer of cytosolic acetyl-CoA
-
-
-
ATP + acetate + CoA
?
show the reaction diagram
-
enzyme plays an important role in the oxidative part of the aceticlastic reaction
-
-
-
ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
show the reaction diagram
Aliivibrio fischeri ES114
-
gene acs encoding the enzyme is regulated by quorum sensing, and acs regulation plays a role in symbiosis, overview
-
-
?
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
Roseovarius sp.
-
aerobic taurine dissimilation via acetate kinase and acetate-CoA ligase. Acetate-CoA ligase operates at the end of the pathway
-
-
?
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
-
nucleocytosolic acetyl-coenzyme a synthetase is required for histone acetylation and global transcription. Acs2p is the major acetyl-CoA source for HATs in glucose
-
-
?
ATP + propionate + CoA
AMP + diphosphate + propionyl-CoA
show the reaction diagram
-
aerobic taurine dissimilation via acetate kinase and acetate-CoA ligase. Acetate-CoA ligase operates at the end of the pathway
-
-
?
CheY + acetyl-CoA + ATP
acetyl-CheY + CoA + AMP + diphosphate
show the reaction diagram
-
CheY is the the excitatory response regulator in the chemotaxis system of Escherichia coli, acetyl-CoA synthetase-catalyzed transfer of acetyl groups from acetate to CheY and autocatalyzed transfer from AcCoA, mechanism, overview
-
-
?
dATP + acetate + CoA
dAMP + diphosphate + acetyl-CoA
show the reaction diagram
Q99NB1
AceCS2 plays a role in the production of energy under ketogenic conditions, such as starvation and diabetes. Acetyl-CoAs produced by AceCS2 are utilized mainly for oxidation
-
?
additional information
?
-
-
may contribute to the adenosine 5'-tetraphosphate synthesis and adenosine 5'-pentaphosphate synthesis during yeast sporulation
-
-
-
additional information
?
-
-
the enzyme can catalyze the activation to their CoA thioesters of some of the side-chain precursors required in Penicillium chrysogenum and Aspergillus nidulans for the production of several penicillins
-
-
-
additional information
?
-
-
acetate thiokinase is not involved in autotrophic CO2 fixation
-
-
-
additional information
?
-
-
CODH/ACS is a bifunctional enzyme that is responsible for the reduction of CO2 to CO and subsequent assembly of acetyl-CoA, as part of the Wood-Ljungdahl carbon fixation pathway, the enzyme is a key player in the global carbon cycle
-
-
-
additional information
?
-
-
metabolic connection between acetate utilization and cell density
-
-
-
additional information
?
-
Q9LTG4
role of ACS in destroying fermentative intermediates
-
-
-
additional information
?
-
-
the acetyltransferase enzyme, AcuA, controls the activity of the acetyl coenzyme A synthetase, AcsA, by acetylating residue Lys549, overview
-
-
-
additional information
?
-
Aliivibrio fischeri ES114
-
metabolic connection between acetate utilization and cell density
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
10 mM, can replace Mg2+ in activation, with 30% of the efficiency relative to Mg2+
Ca2+
-
two types of divalent metal ion requirement, 1. Mg2+, Mn2+, Fe2+, Co2+ or Ca2+ required for the formation of the enzyme-bound acetyl adenylate, 2. Ni2+, Cd2+, Fe2+ or Cu2+ required for adenylate binding
Ca2+
-
can replace Mg2+ in activation, with 50% of the efficiency relative to MgCl2; Km for CaCl2 is 1.2 mM
Ca2+
-
about 70% of the activation with Mg2+ or Mn2+, AF-ACS2
Ca2+
Q2XNL6
about 30% of the activation with Mg2+ or Mn2+
Cd2+
-
two types of divalent metal ion requirement, 1. Mg2+, Mn2+, Fe2+, Co2+ or Ca2+ required for the formation of the enzyme-bound acetyl adenylate, 2. Ni2+, Cd2+, Fe2+ or Cu2+ required for adenylate binding
Co2+
-
two types of divalent metal ion requirement, 1. Mg2+, Mn2+, Fe2+, Co2+ or Ca2+ required for the formation of the enzyme-bound acetyl adenylate, 2. Ni2+, Cd2+, Fe2+ or Cu2+ required for adenylate binding
Co2+
-
can replace Mg2+ in activation, 50% as effective as MgCl2, Km for CoCl2 is 0.2 mM
Co2+
-
about 70% of the activation with Mg2+ or Mn2+, AF-ACS2
Co2+
Q2XNL6
about 80% of the activation with Mg2+ or Mn2+
Cu2+
-
two types of divalent metal ion requirement, 1. Mg2+, Mn2+, Fe2+, Co2+ or Ca2+ required for the formation of the enzyme-bound acetyl adenylate, 2. Ni2+, Cd2+, Fe2+ or Cu2+ required for adenylate binding
Fe2+
-
two types of divalent metal ion requirement, 1. Mg2+, Mn2+, Fe2+, Co2+ or Ca2+ required for the formation of the enzyme-bound acetyl adenylate, 2. Ni2+, Cd2+, Fe2+ or Cu2+ required for adenylate binding
Fe2+
-
CODH/ACS uses a Ni-Fe-S center called the C-cluster to reduce carbon dioxide to carbon monoxide and uses a second Ni-Fe-S center, called the A-cluster, to assemble acetyl-CoA from a methyl group, coenzyme A, and C-cluster-generated CO
Fe2+
-
the enzyme contains a ([Fe4S4]2+ Nip2+ Nid2+) cluster in the alpha-subunit, bifunctional Ni-Fe-S containing ACS/CODH
Fe2+
-
the enzyme contains a ([Fe4S4]2+ Nip2+ Nid2+) cluster in the alpha-subunit, exchange coupling pathway between the Sc = 1/2 [Fe4S4]1+ cluster and the SNi = 1/2 Nip 1+ involves the cysteinate that links one cluster site, previously labeled FeD, to the Ni1+, structure and spectral analysis, overview
Fe2+
-
the A-cluster of acetyl-coenzyme A synthase consists of an [Fe4S4] cubane bridged to a [NipNid] centre via C509 cysteinate. The bridging cysteinate, which can be substituted by histidine imidazole, mediates communication between the [Fe4S4] cubane and the [NipNid] centre during the synthesis of acetyl-CoA
K+
-
absolute requirement for a monovalent cation, stimulates, Km: 14.3 mM, inhibition above 0.1 M
K+
-
activates, absolute requirement for certain monovalent cations, no inhibition at high concentrations
K+
-
KCl increases the activity of the enzyme about 60% at 5 mM and 80% at 20 mM
KCl
-
optimal activity at 1-1.5 M
Li+
-
activation at 5-8 mM, absolute requirement for certain monovalent cations, inhibition above 10 mM
Mg2+
-
required
Mg2+
-
Km: 4.0 mM; required
Mg2+
-
inhibition above 7 mM; Km: 0.9 mM; required
Mg2+
-
required; two types of divalent metal ion requirement, 1. Mg2+, Mn2+, Fe2+, Co2+ or Ca2+ required for the formation of the enzyme-bound acetyl adenylate, 2. Ni2+, Cd2+, Fe2+ or Cu2+ required for adenylate binding
Mg2+
-
inhibition at high concentrations where the metal is present as the free ion; Km for MgCl2 is 0.3 mM; required
Mg2+
-
required
Mg2+
-
MgATP2- is the actual substrate
Mg2+
-
optimal concentration: 5 mM in presence of 1.25 mM NaCl
Mg2+
-
AF-ACS2 shows strong preference for Mg2+ and Mn2+ as the divalent metal
Mg2+
Q2XNL6
strong preference for Mg2+ and Mn2+ as the divalent metal
Mn2+
-
10 mM, 90% of the activation relative to Mg2+
Mn2+
-
10 mM, 38% of the activity relative to Mg2+. Progressive inactivation of the enzyme by MnCl2 is not reversible by subsequent addition of MgCl2
Mn2+
-
5 mM, 94% of the activation relative to Mg2+
Mn2+
-
two types of divalent metal ion requirement, 1. Mg2+, Mn2+, Fe2+, Co2+ or Ca2+ required for the formation of the enzyme-bound acetyl adenylate, 2. Ni2+, Cd2+, Fe2+ or Cu2+ required for adenylate binding
Mn2+
-
can replace Mg2+ in activation; Km for MnCl2 is 0.5 mM
Mn2+
-
64% of the activation relative to Mg2+; can replace Mg2+ in activation
Mn2+
-
AF-ACS2 shows strong preference for Mg2+ and Mn2+ as the divalent metal
Na+
-
absolute requirement for a monovalent cation, poor activator, Km: 33 mM, no inhibition at higher concentrations
Na+
-
activation at 5-8 mM, absolute requirement for certain monovalent cations, inhibition above 10 mM
NH4+
-
absolute requirement for a monovalent cation, stimulates, Km: 14.3 mM, inhibition above 0.1 M
NH4+
-
activates, absolute requirement for certain monovalent cations, no inhibition at high concentrations
NH4+
-
increases the activity by 30% at 5 mM and 70% at 20 mM
Ni
-
nickel-containing bimetallic site, the bifunctional enzyme carbon monoxide dehydrogenase/acetyl-coenzyme A synthase
Ni2+
-
two types of divalent metal ion requirement, 1. Mg2+, Mn2+, Fe2+, Co2+ or Ca2+ required for the formation of the enzyme-bound acetyl adenylate, 2. Ni2+, Cd2+, Fe2+ or Cu2+ required for adenylate binding
Ni2+
-
about 35% of the activation with Mg2+ or Mn2+, AF-ACS2
Ni2+
Q2XNL6
about 25% of the activation with Mg2+ or Mn2+
Ni2+
-
Mssbauer and EPR spectroscopies of alpha-subunit activated with Ni2+
Ni2+
-
activates, the enzyme contains a ([Fe4S4]2+ Nip2+ Nid2+) cluster in the alpha-subunit, bifunctional Ni-Fe-S containing ACS/CODH. Upon incubation in NiCl2, the complete A-cluster assembles, and the isolated a subunit develops approximately 10% of the maximal catalytic activity relative to that of the alpha2beta2 tetramer
Ni2+
-
the enzyme contains a ([Fe4S4]2+ Nip2+ Nid2+) cluster in the alpha-subunit, exchange coupling pathway between the Sc = 1/2 [Fe4S4]1+ cluster and the SNi = 1/2 Nip 1+ involves the cysteinate that links one cluster site, previously labeled FeD, to the Ni1+, structure and spectral analysis, overview
Ni2+
-
the active site of ACS, denoted as the A-cluster, is composed of a redox-active [Fe4-S4] cluster and a dinuclear Ni(II)d-Ni(II)p unit. Synthesis of the dinuclear Ni(II)-Ni(I) complex NiII(N,N'-diethyl-3,7-diazanonane-1,9-dithiolate)NiI(S-2,6-dimesitylphenyl)-(triphenylphosphine) as a Ni(II)d-Ni(I)p model of the A-cluster in acetyl CoA synthase
Ni2+
-
the A-cluster of acetyl-coenzyme A synthase consists of an [Fe4S4] cubane bridged to a [NipNid] centre via C509 cysteinate. The bridging cysteinate, which can be substituted by histidine imidazole, mediates communication between the [Fe4S4] cubane and the [NipNid] centre during the synthesis of acetyl-CoA
Rb+
-
activates, absolute requirement for certain monovalent cations, no inhibition at high concentrations
Tris
-
activates, absolute requirement for certain monovalent cations, no inhibition at high concentrations
Mn2+
Q2XNL6
strong preference for Mg2+ and Mn2+ as the divalent metal
additional information
-
the enzyme uses seven metalloclusters in four reaction steps, overview
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3'-Dephospho-CoASH analogues with a phosphodiester bond
-
-
-
5,5'-dithiobis(2-nitrobenzoate)
-
-
acetyl-CoA
-
competitive to CoASH
ADP
-
competitive to ATP
Allicin
-
reversible noncovalent specific inhibitor of acetyl-CoA synthetase
AMP
-
competitive to ATP
Butyrate
-
propanoate-CoA formation
CO
-
CO inhibits acetyl-CoA synthesis quite strongly and in a cooperative manner
Dicarbonic acid diethyl ester
-
-
diphosphate
-
poor
erythrose 4-phosphate
-
-
glyceraldehyde 3-phosphate
-
weak
glyoxylate
-
-
long-chain acyl-CoA compounds
-
e.g. palmitoyl-CoA, stearoyl-CoA and oleoyl-CoA are potent inhibitors of aerobic enzyme form but not from nonaerobic enzyme form
long-chain acyl-CoA compounds
-
strong
NaCl
-
concentration of 5-20 mM decrease the activity 20-25%
Ni
-
the authors favor a mechanism in which methylation occurs first to Ni(p0 -) or Ni(pI -)[Fe4S4]+, followed by coordination of CO to form Ni(pII)(CO)(CH3) which breaks one of the S(Nid) bonds (forming the bis square planar Ni(II) species, as if the Ni(d)N2S2 unit were acting as a biological pseudodiphosphine, mimicking behavior common to a bidentate phosphine). The CO-insertion/CH3-migration occurs on one metal forming the trigonal planar Ni(pII)-acetyl intermediate. Finally, addition of thiolate produces the thioester. The authors disfavor the unprecedented bimetallic, CO-insertion/CH3-migration mechanism (both in its diamagnetic and paramagnetic guise) and disfavors CO, CH3+, or thiolate (CoA) binding to the distal Ni. Finally, Ni in the proximal site produces a better catalyst than does Cu
Nonidet P40
-
weak
O2
-
the enzyme is O2-sensitive
p-chloromercuribenzoate
-
-
p-hydroxymercuribenzoate
-
inhibition is reversible by either CoA or mercaptoethanol
P1,P5-di(adenosine-5)pentaphosphate
-
inhibits ADP formation
palmitoyl-CoA
-
noncompetitive with respect to both acetate and CoA , inhibits adenosine 5-tetraphosphate synthesis
Propanoate
-
butyryl-CoA formation
pyridoxal 5'-phosphate
-
-
Seleno-CoA
-
competitive to CoA
Short-chain CoA esters
-
-
-
Tween 100
-
-
-
Xylulose 5-phosphate
-
-
Monovalent cations
-
at 200 mM
-
additional information
-
antiserum prepared against the aerobic isoenzyme inhibits the homologous enzyme activity but shows no effect on nonaerobic acetyl-CoA synthetase activity
-
additional information
-
aerobic and non-aerobic enzyme form: antibody directed towards one protein precipitated and inhibits the activity of the homologous, but not of the heterologous enzyme
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
stimulates
acetate
-
required for ATP-diphosphate exchange
acetate
-
required for ATP-diphosphate exchange
acetate
-
stimulates adenosine 5-tetraphosphate synthesis
CobB Sir2 protein
-
activation of the acetylated enzyme requires the nicotinamide adenine dinucleotide-dependent protein deacetylase activity of the CobB Sir2 protein
-
reduced ferredoxin
-
required
SIR2 protein
-
short-chain fatty acid activation by acyl-coenzyme A synthetases requires SIR2 protein function
-
SIRT1
-
AceCS1 is completely inactivated upon acetylation and is rapidly reactivated by SIRT3 deacetylation
-
SIRT3
-
AceCS2 is completely inactivated upon acetylation and is rapidly reactivated by SIRT3 deacetylation
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
29.2
-
2-methylvalerate
-
65C, mutant enzyme W416G
7.6
-
4-methylvalerate
-
65C, mutant enzyme W416G
0.073
-
acetate
Q9NR19
-
0.14
-
acetate
-
pH 6.7, 200 mM K+
0.14
-
acetate
-
CoA
0.146
-
acetate
-
-
0.16
-
acetate
-
-
0.16
-
acetate
-
pH 8.0
0.208
-
acetate
-
-
0.22
-
acetate
-
CoA, in Tris buffer, pH 8.3, 200 mM K+
0.25
-
acetate
-
-
0.37
-
acetate
-
-
0.513
-
acetate
-
-
0.625
-
acetate
-
pH 7.5, 55C, wild-type enzyme
0.65
-
acetate
-
-
0.86
-
acetate
-
-
1.7
-
acetate
-
AF-ACS2
2.61
-
acetate
-
-
3.5
-
acetate
-
65C, wild-type enzyme
4
10
acetate
-
mutant L641P, pH not specified in the publication, temperature not specified in the publication
5.7
-
acetate
-
-
13.2
-
acetate
-
65C, mutant enzyme V388A
24.6
-
acetate
-
65C, mutant enzyme I312A
41
-
acetate
-
wild-type Acs, pH not specified in the publication, temperature not specified in the publication
132.1
-
acetate
-
65C, mutant enzyme W416G
164.4
-
acetate
-
65C, mutant enzyme V388G
596
-
acetate
-
65C, mutant enzyme T313K
11000
-
acetate
-
mutant G266S, pH not specified in the publication, temperature not specified in the publication
0.0037
-
acetyl-CoA
-
pH 7.5, 80C, wild-type alpha-subunit
0.0039
-
acetyl-CoA
-
pH 7.5, 55C, wild-type enzyme
0.0042
-
acetyl-CoA
-
pH 7.5, 80C, wild-type enzyme
0.026
-
acetyl-CoA
-
pH 8.0
0.066
-
acetyl-CoA
-
-
1.8
-
acetyl-CoA
-
-
5.26
-
Acrylate
-
-
0.093
-
ADP
-
pH 7.5, 55C, wild-type enzyme
0.017
-
ATP
-
in Tris buffer, pH 6.7, 200 mM K+
0.0224
-
ATP
-
pH 7.5, mutant enzyme R526A
0.0238
-
ATP
-
pH 7.5, mutant enzyme A357V
0.0265
-
ATP
-
pH 7.5, mutant enzyme R584E
0.0287
-
ATP
-
pH 7.5, mutant enzyme R194A
0.0373
-
ATP
-
pH 7.5, mutant enzyme R194E
0.0381
-
ATP
-
pH 7.5, mutant enzyme R584A
0.044
-
ATP
-
pH 7.5, mutant enzyme D517P
0.0638
-
ATP
-
pH 7.5, mutant enzyme G524S
0.0771
-
ATP
-
pH 7.5, wild-type enzyme
0.1
-
ATP
-
in Pipes buffer, pH 6.7, 200 mM K+
0.16
-
ATP
-
synthesis of adenosine 5-tetraphosphate
0.221
-
ATP
-
pH 7.5, 55C, wild-type enzyme
0.243
-
ATP
-
pH 7.5, mutant enzyme D517G
0.245
-
ATP
Q9NR19
-
0.25
-
ATP
-
-
0.35
-
ATP
-
Tris buffer, pH 8.3, 200 mM K+
0.36
-
ATP
-
-
0.52
-
ATP
-
pH 8.0
0.71
-
ATP
-
-
2.9
-
ATP
-
AF-ACS2
0.46
-
Butyrate
-
65C, mutant enzyme T313V
6.8
-
Butyrate
-
-
39.2
-
Butyrate
-
65C, mutant enzyme W416G
133
-
Butyrate
-
AF-ACS2
151.9
-
Butyrate
-
65C, mutant enzyme V388A
0.011
-
CoA
Q9NR19
-
0.0139
-
CoA
-
pH 7.5, 55C, wild-type enzyme
0.05
-
CoA
-
value above 0.05 mM
0.05
-
CoA
-
pH 7.5, wild-type enzyme
0.104
-
CoA
-
-
0.1072
-
CoA
-
pH 7.5, mutant enzyme R194E
0.133
-
CoA
-
pH 7.5, mutant enzyme A357V
0.1417
-
CoA
-
pH 7.5, mutant enzyme R194A
0.18
-
CoA
-
65C, mutant enzyme I312A; 65C, mutant enzyme V388G
0.19
-
CoA
-
65C, wild-type enzyme
0.205
-
CoA
-
pH 7.5, mutant enzyme R526A
0.21
-
CoA
-
-
0.228
-
CoA
-
pH 7.5, mutant enzyme D517G
0.28
-
CoA
-
in Tris buffer, pH 6.7, 200 mM K+
0.3
-
CoA
-
AF-ACS2
0.35
-
CoA
-
65C, mutant enzyme V388A
0.3583
-
CoA
-
pH 7.5, mutant enzyme R584A
0.426
-
CoA
-
pH 7.5, mutant enzyme R584E
0.43
-
CoA
-
65C, mutant enzyme W416G
0.448
-
CoA
-
pH 7.5, mutant enzyme G524S
0.527
-
CoA
-
pH 7.5, mutant enzyme D517P
0.7
-
CoA
-
65C, mutant enzyme T313V
1.2
-
CoA
-
in Pipes buffer, pH 6.7, 200 mM K+
31.2
-
fluoroacetate
-
-
10.2
-
Heptanoate
-
65C, mutant enzyme W416G
6.1
-
Hexanoate
-
65C, mutant enzyme W416G
0.65
-
MgATP2-
-
65C, mutant enzyme T313V
2.3
-
MgATP2-
-
65C, mutant enzyme W416G
2.6
-
MgATP2-
-
65C, mutant enzyme V388A
3.3
-
MgATP2-
-
65C, wild-type enzyme
3.4
-
MgATP2-
-
65C, mutant enzyme T313K
4
-
MgATP2-
-
65C, mutant enzyme V388G
18.1
-
Octanoate
-
65C, mutant enzyme W416G
0.23
-
phosphate
-
pH 7.5, 80C, wild-type enzyme
0.272
-
phosphate
-
pH 7.5, 55C, wild-type enzyme
3.1
-
Propanoate
-
-
8.3
-
Propanoate
-
-
9
-
Propanoate
-
-
10.5
-
Propanoate
-
-
3.9
-
Propionate
-
AF-ACS2
4.1
-
Propionate
-
65C, mutant enzyme V388A
4.5
-
Propionate
-
65C, mutant enzyme T313V
36.5
-
Propionate
-
65C, wild-type enzyme
128.6
-
Propionate
-
65C, mutant enzyme V388G
188.8
-
Propionate
-
65C, mutant enzyme W416G
4.7
-
tripolyphosphate
-
synthesis of adenosine 5-tetraphosphate
11.1
-
valerate
-
65C, mutant enzyme W416G
6.6
-
MgATP2-
-
65C, mutant enzyme I312A
additional information
-
additional information
-
-
-
additional information
-
additional information
-
kinetics and extent of reduction of the Fe4S4 cubane in the apo-alpha subunit and the Ni-activated a subunit upon exposure to titanium(III) citrate, detailed overview
-
additional information
-
additional information
-
kinetic parameters of wild type and mutant enzymes at 55C, overview
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.67
-
2-methylvalerate
-
65C, mutant enzyme W416G
10.9
-
4-methylvalerate
-
65C, mutant enzyme W416G
1.9
-
acetate
-
65C, mutant enzyme T313K
21.2
-
acetate
-
AF-ACS2
30.4
-
acetate
-
65C, mutant enzyme I312A
31.9
-
acetate
-
65C, mutant enzyme V388G
33.7
-
acetate
-
65C, mutant enzyme W416G
36.2
-
acetate
-
65C, mutant enzyme V388A
65.4
-
acetate
-
65C, wild-type enzyme
1500
-
acetate
-
mutant L641P, pH not specified in the publication, temperature not specified in the publication
3200
-
acetate
-
mutant G266S, pH not specified in the publication, temperature not specified in the publication
9400
-
acetate
-
wild-type Acs, pH not specified in the publication, temperature not specified in the publication
1.7
-
ATP
-
pH 7.5, wild-type enzyme
13.2
-
ATP
-
AF-ACS2
36.4
-
ATP
-
pH 7.5, mutant enzyme R584E
37.4
-
ATP
-
pH 7.5, mutant enzyme R526A
38.9
-
ATP
-
pH 7.5, mutant enzyme A357V
39.9
-
ATP
-
pH 7.5, mutant enzyme R194A
40.9
-
ATP
-
pH 7.5, mutant enzyme D517P
41.7
-
ATP
-
pH 7.5, mutant enzyme R194E
42.8
-
ATP
-
pH 7.5, mutant enzyme D517G
46.7
-
ATP
-
pH 7.5, mutant enzyme R584A
49.8
-
ATP
-
pH 7.5, mutant enzyme G524S
100.6
-
ATP
-
pH 7.5, wild-type enzyme
0.013
-
Butyrate
-
AF-ACS2
1.56
-
Butyrate
-
65C, mutant enzyme V388A
3.4
-
Butyrate
-
65C, mutant enzyme T313V
10.8
-
Butyrate
-
65C, mutant enzyme W416G
3.2
-
CoA
-
pH 7.5, wild-type enzyme
35
-
CoA
-
pH 7.5, mutant enzyme A357V
40
-
CoA
-
pH 7.5, mutant enzyme R194E
40.5
-
CoA
-
pH 7.5, mutant enzyme R526A
40.8
-
CoA
-
pH 7.5, mutant enzyme R584E
41.1
-
CoA
-
pH 7.5, mutant enzyme R194A
41.5
-
CoA
-
pH 7.5, mutant enzyme R584A
42.4
-
CoA
-
pH 7.5, mutant enzyme D517G
43.1
-
CoA
-
pH 7.5, mutant enzyme G524S
43.8
-
CoA
-
pH 7.5, mutant enzyme D517P
95.1
-
CoA
-
pH 7.5, wild-type enzyme
144.9
-
CoA
-
AF-ACS2
7.3
-
Heptanoate
-
65C, mutant enzyme W416G
5.9
-
Hexanoate
-
65C, mutant enzyme W416G
3.3
-
Octanoate
-
65C, mutant enzyme W416G
5.9
-
Propionate
-
65C, mutant enzyme T313V
6
-
Propionate
-
65C, mutant enzyme V388G
9.1
-
Propionate
-
AF-ACS2
13.2
-
Propionate
-
65C, mutant enzyme V388A
19.2
-
Propionate
-
65C, mutant enzyme W416G
46.3
-
Propionate
-
65C, wild-type enzyme
11.9
-
valerate
-
65C, mutant enzyme W416G
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.29
-
acetate
-
mutant G266S, pH not specified in the publication, temperature not specified in the publication
6109
3.6
-
acetate
-
mutant L641P, pH not specified in the publication, temperature not specified in the publication
6109
229
-
acetate
-
wild-type Acs, pH not specified in the publication, temperature not specified in the publication
6109
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2.7
-
acetyl-CoA
-
pH 8.0
12
-
ADP
-
pH 8.0
15
-
AMP
-
pH 8.0
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
Ni-activated A110C mutant alpha subunit at 1 atm CO
8.1
-
-
Ni-activated A222L mutant alpha subunit at 1 atm CO
11.9
-
Q99NB1
AceCS2
13.4
-
-
formation of acetyl-CoA
26.8
-
Q99NB1
AceCS1
additional information
-
-
-
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.2
-
-
CO/acetyl-CoA exchange assay at
6.3
-
-
adenosine tetraphosphate synthesis
7.5
-
-, Q6EMJ3
-
7.5
-
-
assay at
7.5
-
-
assay at
8
-
-
ATP-diphosphate exchange
8.3
10.2
-
in 25 mM KCl buffer
8.5
-
-
-
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
8.5
-
pH 5.5: about 60% of maximal activity, pH 8.5: about 50% of maximal activity
6
10.5
-
6: about 50% of maximal activity, 10.5: about 60% of activity maximum
6
9.7
-
6.0: about 45% of maximal activity, 9.7: about 70% of maximal activity
6.5
8.5
-
30-40% of maximal activity at pH 6.5 and 8.5
6.8
10.1
-
about 50% of maximal activity at pH 6.8 and pH 10.1
6.8
8.8
-
about 50% of maximal activity at pH 6.8 and 8.8
7.3
8.1
-
90% of maximal activity at pH 7.3 and 8.1
7.5
10
-
7.5: about 50% of maximal activity, 10.0: about 70% of maximal activity
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
27
-
-
CO/acetyl-CoA exchange assay at
38
-
-, Q6EMJ3
-
55
-
-
phosphorylation and phosphorolysis assays at
65
70
-
AF-ACS2
80
-
-
arsenolytic assay at and temperature optimum
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
20
50
-
20C: about 45% of maximal activity, 50C: about 30% of maximal activity
45
75
Q2XNL6
45C: about 55% of maximal activity, 75C: about 50% of maximal activity
45
85
-
45C: about 55% of maximal activity, 85C: about 60% of maximal activity, AF-ACS2
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
Q99NB1
marked induction of AceCS1 mRNA and protein during differentiation of 3T3-L1 cells, neither AceCS2 mRNA nor protein is detected in undifferentiated or differentiated 3T3-L1 cells
Manually annotated by BRENDA team
-
cells express higher levels of cytosolic acetyl-CoA synthetase ACSS2 under hypoxia than normoxia. Knockdown of ACSS2 by RNA interference in tumor cells enhances tumor cell death under long-term hypoxia in vitro. The ACSS2 suppression slows tumor growth in vivo. Tumor cells excrete acetate and the quantity increases under hypoxia, the pattern of acetate excretion follows the expression pattern of ACSS2. The ACSS2 knockdown leads to a corresponding reduction in the acetate excretion in tumor cells
Manually annotated by BRENDA team
-
from Glycine max L. cv. Williams inoculated with Bradyrhizobium japonicum
Manually annotated by BRENDA team
Q99NB1
AceCS2, low activity
Manually annotated by BRENDA team
-
cells express higher levels of cytosolic acetyl-CoA synthetase ACSS2 under hypoxia than normoxia. Knockdown of ACSS2 by RNA interference in tumor cells enhances tumor cell death under long-term hypoxia in vitro. The ACSS2 suppression slows tumor growth in vivo. Tumor cells excrete acetate and the quantity increases under hypoxia, the pattern of acetate excretion follows the expression pattern of ACSS2. The ACSS2 knockdown leads to a corresponding reduction in the acetate excretion in tumor cells
Manually annotated by BRENDA team
-
cells express higher levels of cytosolic acetyl-CoA synthetase ACSS2 under hypoxia than normoxia. Knockdown of ACSS2 by RNA interference in tumor cells enhances tumor cell death under long-term hypoxia in vitro. The ACSS2 suppression slows tumor growth in vivo. Tumor cells excrete acetate and the quantity increases under hypoxia, the pattern of acetate excretion follows the expression pattern of ACSS2. The ACSS2 knockdown leads to a corresponding reduction in the acetate excretion in tumor cells
Manually annotated by BRENDA team
-
Sigma and Boehringer Mannheim
Manually annotated by BRENDA team
Q99NB1
AceCS2, high activity
Manually annotated by BRENDA team
Q99NB1
AceCS2, high activity
Manually annotated by BRENDA team
-
from plants with altered ACS levels
Manually annotated by BRENDA team
-
1.5fold-2fold higher activity of the enzyme in the periportal zone of the male rat liver compared with the perivenous zone in the fed state, but not in the fasted/refed state
Manually annotated by BRENDA team
Q99NB1
AceCS1, no AceCS2 activity
Manually annotated by BRENDA team
-
cells express higher levels of cytosolic acetyl-CoA synthetase ACSS2 under hypoxia than normoxia. Knockdown of ACSS2 by RNA interference in tumor cells enhances tumor cell death under long-term hypoxia in vitro. The ACSS2 suppression slows tumor growth in vivo. Tumor cells excrete acetate and the quantity increases under hypoxia, the pattern of acetate excretion follows the expression pattern of ACSS2. The ACSS2 knockdown leads to a corresponding reduction in the acetate excretion in tumor cells
Manually annotated by BRENDA team
-
newly-pupated pupae of both sexes
Manually annotated by BRENDA team
Q99NB1
AceCS2, high activity
Manually annotated by BRENDA team
Q99NB1
AceCS2, high activity
Manually annotated by BRENDA team
Q99NB1
AceCS2, high activity
Manually annotated by BRENDA team
Q99NB1
AceCS2, high activity
Manually annotated by BRENDA team
additional information
Q99NB1
no AceCS2 activity is detected in liver. Marked induction of AceCS1 mRNA and protein during differentiation of 3T3-L1 cells, neither AceCS2 mRNA nor protein is detected in undifferentiated or differentiated 3T3-L1 cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
isoform ACS2 is localized primarily to the nucleus, with a minor amount in the cytosol
Manually annotated by BRENDA team
Q99NB1
matrix, AceCS2
Manually annotated by BRENDA team
-
isoform ACS2 is localized primarily to the nucleus, with a minor amount in the cytosol
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
58000
-
-
gel filtration
60000
-
-
gel filtration
72000
-
-
gel filtration
80000
-
Q9NR19
gel filtration
139000
-
-
gel filtration
141000
-
-, Q6EMJ3
gel filtration
144800
-
Q2XNL6
gel filtration
148000
-
-
gel filtration
150000
-
-
gel filtration
151000
-
-
sedimentation equilibrium analysis
221200
-
-
AF-ACS2, gel filtration
250000
-
-
low speed sedimentation without reaching equilibrium
251200
-
-
gel filtration
261800
-
-
ultracentrifugal studies, sedimentation equilibrium absorption optics
610000
-
-
analytical ultracentrifugation
625000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 80500, SDS-PAGE, aerobic isoenzyme
?
-
x * 78000, SDS-PAGE
?
-
-
?
Q9BEA3
x * 74309, calculation from nucleotide sequence
?
Q99NB1
x * 71000, AceCS2, SDS-PAGE; x * 74662, AceCS2, calculation from nucleotide sequence; x * 78000, AceCS1, SDS-PAGE
?
Saccharomyces cerevisiae LK2G12
-
x * 80500, SDS-PAGE, aerobic isoenzyme
-
dimer
-
2 * 72000, SDS-PAGE
dimer
-
2 * 73000, SDS-PAGE
dimer
-
2 * 70000, SDS-PAGE
dimer
Q2XNL6
2 * 71556, calculated from sequence
dimer
-, Q6EMJ3
2 * 70000, SDS-PAGE
heterotetramer
-
alpha2beta2
monomer
-
x * 77000, SDS-PAGE
monomer
Q9NR19
1 * 78000, SDS-PAGE
octamer
-
8 * 75000, SDS-PAGE
tetramer
-
alpha2beta2
tetramer
-
acetyl-coenzyme A synthase/carbon monoxide dehydrogenase is an alpha2beta2 tetramer, alpha-subunit structure, overview
tetramer
-
acetyl-coenzyme A synthase/carbon monoxide dehydrogenase is an alpha2beta2 tetramer, structure analysis, overview
trimer
-
3 * 82500-83500, SDS-PAGE
trimer
-
3 * 77587, AF-ACS2, calculated from sequence
trimer
Saccharomyces cerevisiae LK2G12
-
3 * 82500-83500, SDS-PAGE
-
monomer
-
1 * 89000, SDS-PAGE
additional information
-
Moorella thermoacetica CODH/ACS contains a very long enzyme channel to allow for intermolecular CO transport, overview
additional information
-
the beta2 subunits are solely responsible for catalyzing the CODH reaction
additional information
-
structural analysis by circular dichroism spectroscopy and structure modelling, comparison of domain organization of subunits to succinyl-CoA synthetases, EC 6.2.1.5, overview
additional information
-
the active site of ACS, denoted as the A-cluster, is composed of a redox-active [Fe4-S4] cluster and a dinuclear Ni(II)dNi(II)p unit. Synthesis of the dinuclear Ni(II)-Ni(I) complex NiII(N,N'-diethyl-3,7-diazanonane-1,9-dithiolate)NiI(S-2,6-dimesitylphenyl)-(triphenylphosphine) as a Ni(II)d-Ni(I)p model of the A-cluster in acetyl CoA synthase
additional information
-
the A-cluster of acetyl-coenzyme A synthase consists of an [Fe4S4] cubane bridged to a [NipNid] centre via C509 cysteinate. The bridging cysteinate, which can be substituted by histidine imidazole, mediates communication between the [Fe4S4] cubane and the [NipNid] centre during the synthesis of acetyl-CoA. The ACS/CODH from Moorella thermoacetica is an alpha2beta2 tetramer containing seven metal clusters connected by a molecular tunnel network, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
side-chain modification
-
the acetyltransferase enzyme, AcuA, controls the activity of the acetyl coenzyme A synthetase, AcsA, by acetylating residue Lys549, overview
proteolytic modification
Q99NB1
the putative mitochondrial targeting signal is cleaved during the transportation of the enzyme into the mitochondria matrix
acetylation
-
posttranslational regulation by acetylation of Lys609. Acetylation blocks synthesis of the adenylate intermediate but does not affect the thioester-forming activity of the enzyme
acetylation
-
the enzyme is regulated by a Sir2-dependent protein acetylation/deacetylation system. Leu641 is critical for the acetylation of the enzyme by protein acetyltransferase.Mutation at Leu641 prevents the acetylation of Acs by protein acetyltransferase and maintains the acetyl-coenzyme A synthetase in its active state
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
sitting drop vapor diffusion method, 2.3 A resolution, residues 72-713 of ACS (subcloned into expression vector pET28a and expressed in Escherichia coli) in complex with AMP
Q01574
vapor diffusion method, crystallographic structures of wild-type enzyme and mutant enzymes R194A, R584A, R584E, K609A, and V386A
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
60
-
-
5 min, 20% loss of activity
90
-
-
120 min, stable
98
-
-
half-life: 72 min
100
-
-
half-life: 8 min. Addition of 1 M (NH4)2SO4 stabilizes the enzyme to a half-life of 24 min
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
denatured upon freezing
-
ATP and glycerol stabilize during storage at 0-4C
-
photoinactivation in presence of methylene blue
-
particularly sensitive to repeated freezing
-
KCl stabilizes
-
ATP and AMP stabilize
-
freezing and thawing causes loss of activity
-
more than 90% loss of activity in solutions of low ionic strength, for 20 min, at 0-4C or at room temperature
-
storage stability is enhanced by high salt and protein concentration
-
OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
the enzyme is O2-sensitive
-
687824
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4C, 0.1 M buffer, pH 7.5, 3 mM mercaptoethanol, stable for several weeks
-
4C, 20% w/v glycerol, stable for 1 month
-
0-4C, 20 mM Tris/Hcl, pH 8.0, 10 mM ATP, 5 mM MgCl2, 1 mM DTT or 5 mM 2-mercaptoethanol, 20% glycerol, stable for at least 1 month
-
-20C, stable for several months
-
-20C, cannot be stored for more than 3 days without a considerable loss of activity
-
-20C, 0.2 mM DTT, stable for at least one month
-
-20C, 0.5 M potassium phosphate, pH 7.5, 7 mM 2-mercaptoethanol and 0.5 mM EDTA, protein concentration above 5 mg/ml, no loss of activity after 6 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-
Q9NR19
recombinant C-terminally His-tagged ACS from Escherichia coli strain BL21(DE3) by nickel affinity chromatography under anaerobic conditions
-
partial
-
recombinant enzyme
-
recombinant alpha and beta subunits from Escherichia coli strain BL21(DE3) by heat tteatment at 90C for 30 min, hydrophobic interaction chromatography, and gel filtration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli, AF-ACS2
-
acetyl-CoA synthetase overexpression in Escherichia coli demonstrates more efficient acetate assimilation and lower acetate accumulation
-
overexpression in Escherichia coli
-
expression in Escherichia coli
Q9NUB1
production in HEK -293 cells
Q9NR19
expression in Escherichia coli
-
expression of alpha-subunit in Escherichia coli
-
expression of C-terminally His-tagged ACS in Escherichia coli strain BL21(DE3)
-
expression in Escherichia coli
-
genes acdIa and acdIb encoding the alpha and beta subunits, expression in Escherichia coli strain BL21(DE3)
-
residues 72-713 of ACS are subcloned into expression vector pET28a and expressed in Escherichia coli
Q01574
10-deacetylbaccatin III 10beta-O-acetyltransferase (DBAT) from Taxus can catalyze the transfer of acetyl, propionyl or n-butyryl from CoA to the C10-hydroxyl of 10-deacetylbaccatin III. Escherichia coli JM109 are transformed to recombinantly express dbat, and this enzyme function is coupled to that of acetyl-CoA synthase expressed from and regulated by genes encoded on the bacterial chromosome
Taxus sp.
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression of CO dehydrogenase/acetyl coenzyme A synthase in Methanosarcina spp. is coordinately regulated in response to substrate by differential transcription initiation and early elongation termination near the 3' end of a 371-bp leader sequence
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
I312A
-
kcat/Km for acetate is 15fold lower than wild-type value, kcat/Km for propionate is 5.2fold lower than wild-type value. Mutant enzyme shows activity with butyrate
T313K
-
Km for acetate is 170fold higher than wild-type value, kcat for acetate is 34fold lower than wild-type value
T313V
-
kcat/Km for acetate is 2.5fold lower than wild-type value, kcat/Km for propionate is identical to wild-type value
V388A
-
kcat/Km for acetate is 6.9fold lower than wild-type value, kcat/Km for propionate is 2.5fold higher than wild-type value, mutant enzyme shows activity with wild-type enzyme
V388G
-
kcat/Km for acetate is 93fold lower than wild-type value, kcat/Km for propionate is 26fold lower than wild-type value
W416G
-
kcat/Km for acetate is 71.5fold lower than wild-type value, kcat/Km for propionate is 13fold lower than wild-type value, mutant enzyme shows activity with: butyrate, valerate, hexanoate, heptanoate, octanoate, 4-methylvalerate and 3-methylvalerate
I312A
Methanothermobacter thermautotrophicus Z245
-
kcat/Km for acetate is 15fold lower than wild-type value, kcat/Km for propionate is 5.2fold lower than wild-type value. Mutant enzyme shows activity with butyrate
-
T313K
Methanothermobacter thermautotrophicus Z245
-
Km for acetate is 170fold higher than wild-type value, kcat for acetate is 34fold lower than wild-type value
-
T313V
Methanothermobacter thermautotrophicus Z245
-
kcat/Km for acetate is 2.5fold lower than wild-type value, kcat/Km for propionate is identical to wild-type value
-
V388A
Methanothermobacter thermautotrophicus Z245
-
kcat/Km for acetate is 6.9fold lower than wild-type value, kcat/Km for propionate is 2.5fold higher than wild-type value, mutant enzyme shows activity with wild-type enzyme
-
V388G
Methanothermobacter thermautotrophicus Z245
-
kcat/Km for acetate is 93fold lower than wild-type value, kcat/Km for propionate is 26fold lower than wild-type value
-
A110C
-
site-directed mutagenesis, alpha-subunit mutant, which does not show cooperative CO inhibition in contrast to the wild-type enzyme
A222L
-
site-directed mutagenesis, alpha-subunit mutant, which does not show cooperative CO inhibition in contrast to the wild-type enzyme
A265M
-
site-directed mutagenesis, alpha-subunit mutant, the recombinantly expressed mutant enzymes cannot be purified
C509A
-
site-directe mutagenesis, mutant C509A shows a significantly diminished methyl transfer activity compared to the wild-type enzyme
C509H
-
site-directed mutagenesis, mutant C509H can accept a methyl group from CH3-Co3+FeSP at over 70% extent. The near-wild-type-level of methyl group transfer activity for C509H indicates that the di-nickel site is assembled well in this mutant, and strongly suggests that an imidazole group can bridge the di-nickel site to the cubane of the A-cluster. Histidine that replaces the bridging cysteine 509 might function as a bridge, with one nitrogen of the imidazole ring coordinating to a cubane Fe and the other nitrogen coordinating to Nip
C509S
-
site-directed mutagenesis, mutant C509S, in which the cysteinate bridge C509 might be replaced by a serine oxide, exhibits no detectable methyl transfer activity. Oxygen is a harder donor than sulfide, and the electronic coupling between the cubane and the di-nickel site may differ relative to sulfide. Absence of methyl transfer activity in C509S indicates that an O bridge is not sufficient for this communication
C509V
-
site-directed mutagenesis, mutant C509V exhibits no detectable methyl group transfer activity due to it lacking a bridging coordinating atom, Val is more bulky and has greater steric hindrance
D212Ebeta
-
site-directed mutagenesis, the mutant shows 2-4% of wild-type activity, slightly impaired in arsenolysis
D212Nbeta
-
site-directed mutagenesis, the mutant shows highly reduced phosphorylation/phosphorolysis activity, but only slightly impaired in arsenolysis
E218Qalpha
-
site-directed mutagenesis, inactive mutant
H257Dalpha
-
site-directed mutagenesis, inactive mutant
A357V
-
kcat/Km for ATP is 1.2fold higher than wild-type value, kcat/Km for CoA is 3.2fold lower than wild-type value
D517G
-
kcat/Km for ATP is 6.5fold lower than wild-type value, kcat/Km for CoA is 9.5fold lower than wild-type value
D517P
-
kcat/Km for ATP is 1.4fold lower than wild-type value, kcat/Km for CoA is 23.7fold lower than wild-type value
G266S
-
random mutagenesis, mutant Km for acetate is 268fold higher than that of the AcsWT enzyme, while kcat is 3fold reduced; the Acs mutant does not cause growth arrest in contrast to the wild-type enzyme
G524L
-
inactive mutant enzyme; mutant enzyme is unable to catalyze the complete reaction yet catalyzes the adenylation half-reaction with activity comparable to the wild-type enzyme
G524S
-
kcat/Km for ATP is 1.6fold lower than wild-type value, kcat/Km for CoA is 19fold lower than wild-type value
K609A
-
inactive mutant enzyme; mutation results in an enzyme that is unable to catalyze the adenylate reaction
K609A
-
random mutagenesis
L641P
-
mutation at Leu641 prevents the acetylation of Acs by protein acetyltransferase and maintains the acetyl-coenzyme A synthetase in its active state
L641P
-
random mutagenesis, mutant Km for acetate is higher than that of the AcsWT enzyme, while kcat is reduced
R194A
-
kcat/Km for ATP is 1.1fold higher than wild-type value, kcat/Km for CoA is 6.3fold lower than wild-type value
R194E
-
kcat/Km for ATP is 1.2fold lower than wild-type value, kcat/Km for CoA is 4.75fold lower than wild-type value
R526A
-
kcat/Km for ATP is 1.2fold higher than wild-type value, kcat/Km for CoA is 9.5fold lower than wild-type value
R584A
-
kcat/Km for ATP is 1.2 fold than wild-type value, kcat/Km for CoA is 19fold lower than wild-type value
R584E
-
kcat/Km for ATP is 1.1fold higher than wild-type value, kcat/Km for CoA is 21fold lower than wild-type value
additional information
-
the acs mutant of Vibrio fischeri is unable to utilize acetate and has a competitive defect when colonizing the squid, indicating the importance of proper control of acetate metabolism in the light of organ symbiosis, acs mutants are not hypermotile
additional information
Aliivibrio fischeri ES114
-
the acs mutant of Vibrio fischeri is unable to utilize acetate and has a competitive defect when colonizing the squid, indicating the importance of proper control of acetate metabolism in the light of organ symbiosis, acs mutants are not hypermotile
-
additional information
Q9LTG4
a constructed acs1 knockout mutant has a disruption in the plastidic acetyl-CoA synthetase gene leading to 90% decreased ACS activity and largely blocked incorporation of exogenous 14C-acetate and 14C-ethanol into fatty acids. Whereas the disruption has no significant effect on the synthesis of bulk seed triacylglycerols, the acs1 plants are smaller and flowered later. The acs1 mutant shows increased sensitivity to exogenous acetate, ethanol, and acetaldehyde compared to wild-type plants, phenotype, overview
H71Abeta
-
site-directed mutagenesis, inactive mutant concerning phosphorylation/phosphorolysis, slightly impaired in arsenolysis
additional information
-
all mutations in the alpha-subunit have dramatic effects on arsenolysis activity, while mutations in the beta-subunit cause only moderate loss of activity
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
acetyl-CoA synthetase appears to be important in acetate uptake and acetate-dependent lipid synthesis for the growth of cancer cells with a low-glycolysis phenotype
analysis
-
colorimetric assay method to measure acetyl-CoA synthetase activity
medicine
-
cells express higher levels of cytosolic acetyl-CoA synthetase ACSS2 under hypoxia than normoxia. Knockdown of ACSS2 by RNA interference in tumor cells enhances tumor cell death under long-term hypoxia in vitro. The ACSS2 suppression slows tumor growth in vivo. Tumor cells excrete acetate and the quantity increases under hypoxia, the pattern of acetate excretion follows the expression pattern of ACSS2. The ACSS2 knockdown leads to a corresponding reduction in the acetate excretion in tumor cells