Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine.

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Starai VJ, Celic I, Cole RN, Boeke JD, Escalante-Semerena JC

Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine.

Science. 2002 Dec 20;298(5602):2390-2.

PubMed ID

12493915 [ View in PubMed

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Abstract

Acetyl-coenzyme A (CoA) synthetase (Acs) is an enzyme central to metabolism in prokaryotes and eukaryotes. Acs synthesizes acetyl CoA from acetate, adenosine triphosphate, and CoA through an acetyl-adenosine monophosphate (AMP) intermediate. Immunoblotting and mass spectrometry analysis showed that Salmonella enterica Acs enzyme activity is posttranslationally regulated by acetylation of lysine-609. Acetylation blocks synthesis of the adenylate intermediate but does not affect the thioester-forming activity of the enzyme. Activation of the acetylated enzyme requires the nicotinamide adenine dinucleotide-dependent protein deacetylase activity of the CobB Sir2 protein from S. enterica. We propose that acetylation modulates the activity of all the AMP-forming family of enzymes, including nonribosomal peptide synthetases, luciferase, and aryl- and acyl-CoA synthetases. These findings extend our knowledge of the roles of Sir2 proteins in gene silencing, chromosome stability, and cell aging and imply that lysine acetylation is a common regulatory mechanism in eukaryotes and prokaryotes.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
ATP	Acetyl-coenzyme A synthetase, cytoplasmic	Protein	Humans	Unknown	Not Available	Details

Polypeptides

Name	UniProt ID
Acetyl-coenzyme A synthetase	Q8ZKF6	Details