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

V J Starai, I Celic, R N Cole, J D Boeke, J C Escalante-Semerena

Department of Bacteriology, University of Wisconsin, Madison, WI 53706-1567, USA.

Science (New York, N.Y.) 2002 Dec 20

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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.

Citation

V J Starai, I Celic, R N Cole, J D Boeke, J C Escalante-Semerena. Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine. Science (New York, N.Y.). 2002 Dec 20;298(5602):2390-2