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

    Research output: Contribution to journalArticle

    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 aryl-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.

    Original languageEnglish (US)
    Pages (from-to)2390-2392
    Number of pages3
    JournalScience
    Volume298
    Issue number5602
    DOIs
    StatePublished - Dec 20 2002

    ASJC Scopus subject areas

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    Starai, V. J., Celic, I., Cole, R. N., Boeke, J. D., & Escalante-Semerena, J. C. (2002). Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine. Science, 298(5602), 2390-2392. https://doi.org/10.1126/science.1077650