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Literature summary for 6.2.1.1 extracted from

  • Han, X.; Shen, L.; Wang, Q.; Cen, X.; Wang, J.; Wu, M.; Li, P.; Zhao, W.; Zhang, Y.; Zhao, G.
    Cyclic AMP inhibits the activity and promotes the acetylation of acetyl-CoA synthetase through competitive binding to the ATP/AMP pocket (2017), J. Biol. Chem., 292, 1374-1384 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 6.2.1.1

Cloned(Commentary)

Cloned (Comment) Organism
gene acs, recombinant expression of His-tagged wild-type and mutant enzymes in Salmonella enterica strain G2466 Salmonella enterica

Crystallization (Commentary)

Crystallization (Comment) Organism
purified recombinant enzyme SeAcs in complex with cAMP and CoA, X-ray diffraction structure determination and analysis at 1.65 A resolution Salmonella enterica

Protein Variants

Protein Variants Comment Organism
D411A site-directed mutagenesis, the mutant SeAcs variant shows a nearly 10fold increased dissociation constant compared to the wild-type enzyme Salmonella enterica
D500A site-directed mutagenesis, the mutant SeAcs variant is defective in cAMP binding Salmonella enterica
additional information cAMP has no effect on acetylation promotion of the mutant SeAcs enzymes Salmonella enterica
N521A site-directed mutagenesis, the mutant SeAcs variant shows a higher dissociation constant compared to the wild-type enzyme Salmonella enterica
Q415A site-directed mutagenesis, the mutant SeAcs variant is defective in cAMP binding Salmonella enterica
R515A site-directed mutagenesis, the mutant SeAcs variant shows a nearly 10fold increased dissociation constant compared to the wild-type enzyme Salmonella enterica
T416A site-directed mutagenesis, the mutant SeAcs variant shows a higher dissociation constant compared to the wild-type enzyme Salmonella enterica
W413A site-directed mutagenesis, the mutant SeAcs variant is defective in cAMP binding Salmonella enterica

Inhibitors

Inhibitors Comment Organism Structure
cAMP cyclic AMP inhibits the activity and promotes the acetylation of acetyl-CoA synthetase through competitive binding to the highly conserved ATP/AMP binding pocket and restrains SeAcs in an open conformation. cAMP directly binds to the enzyme and inhibits its activity in a substrate-competitive manner. cAMP binding increases SeAcs acetylation by simultaneously promoting Pat-dependent acetylation and inhibiting CobB-dependent deacetylation, resulting in enhanced SeAcs inhibition Salmonella enterica

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ reuqired Salmonella enterica

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + acetate + CoA Salmonella enterica
-
 AMP + diphosphate + acetyl-CoA
-
 ?
ATP + acetate + CoA Salmonella enterica G2466
-
 AMP + diphosphate + acetyl-CoA
-
 ?

Organism

Organism UniProt Comment Textmining
Salmonella enterica
-
-
-
Salmonella enterica G2466
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged wild-type and mutant enzymes from Salmonella enterica strain G2466 by nickel affinity chromatography Salmonella enterica

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + acetate + CoA
-
 Salmonella enterica AMP + diphosphate + acetyl-CoA
-
 ?
ATP + acetate + CoA
-
 Salmonella enterica G2466 AMP + diphosphate + acetyl-CoA
-
 ?
additional information activity determination in a coupled assay with myokinase, pyruvate kinase, and lactate dehydrogenase: SeAcs first converts acetate, CoA, and ATP to acetyl-CoA and AMP. Then, myokinase converts AMP to ADP. Pyruvate kinase converts ADP and phosphoenolpyruvate to pyruvate and ATP. Finally, lactate dehydrogenase reduces pyruvate and oxidizes NADH to NAD+ Salmonella enterica ?
-
 ?
additional information activity determination in a coupled assay with myokinase, pyruvate kinase, and lactate dehydrogenase: SeAcs first converts acetate, CoA, and ATP to acetyl-CoA and AMP. Then, myokinase converts AMP to ADP. Pyruvate kinase converts ADP and phosphoenolpyruvate to pyruvate and ATP. Finally, lactate dehydrogenase reduces pyruvate and oxidizes NADH to NAD+ Salmonella enterica G2466 ?
-
 ?

Synonyms

Synonyms Comment Organism
Acetyl-CoA synthetase
-
 Salmonella enterica
acetyl-coenzyme A synthetase
-
 Salmonella enterica
ACS
-
 Salmonella enterica
SeAcs
-
 Salmonella enterica

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Salmonella enterica

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Salmonella enterica

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Salmonella enterica

General Information

General Information Comment Organism
malfunction cyclic AMP inhibits the activity and promotes the acetylation of acetyl-CoA synthetase through competitive binding to the ATP/AMP pocket. cAMP directly binds to the enzyme and inhibits its activity in a substrate-competitive manner. cAMP binding increases SeAcs acetylation by simultaneously promoting Pat-dependent acetylation and inhibiting CobB-dependent deacetylation, resulting in enhanced SeAcs inhibition Salmonella enterica
physiological function the high-affinity biosynthetic pathway for converting acetate to acetyl-coenzyme A (acetyl-CoA) is catalyzed by the central metabolic enzyme acetyl-coenzyme A synthetase (Acs), which is finely regulated both at the transcriptional level via cyclic AMP (cAMP)-driven trans-activation and at the post-translational level via acetylation inhibition. The cAMP contact residues are well conserved from prokaryotes to eukaryotes, suggesting a general regulatory mechanism of cAMP on Acs. cAMP generally inhibits other acyl- or aryl-CoA synthetases Salmonella enterica