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Literature summary 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

Cloned(Commentary)

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

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
6.2.1.1 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

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

Inhibitors

EC Number Inhibitors Comment Organism Structure
6.2.1.1 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

EC Number Metals/Ions Comment Organism Structure
6.2.1.1 Mg2+ reuqired Salmonella enterica

Natural Substrates/ Products (Substrates)

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

Organism

EC Number Organism UniProt Comment Textmining
6.2.1.1 Salmonella enterica
-
-
-
6.2.1.1 Salmonella enterica G2466
-
-
-

Purification (Commentary)

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

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.2.1.1 ATP + acetate + CoA
-
 Salmonella enterica AMP + diphosphate + acetyl-CoA
-
 ?
6.2.1.1 ATP + acetate + CoA
-
 Salmonella enterica G2466 AMP + diphosphate + acetyl-CoA
-
 ?
6.2.1.1 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 ?
-
 ?
6.2.1.1 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

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

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
6.2.1.1 37
-
 assay at Salmonella enterica

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
6.2.1.1 7.5
-
 assay at Salmonella enterica

Cofactor

EC Number Cofactor Comment Organism Structure
6.2.1.1 ATP
-
 Salmonella enterica

General Information

EC Number General Information Comment Organism
6.2.1.1 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
6.2.1.1 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