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

V. J. Starai, I. Celic, Robert 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

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Acetate-CoA Ligase
Acetylation
Lysine
Enzymes
Adenosine Monophosphate
Eukaryota
Peptide Synthases
Coenzyme A Ligases
Chromosomal Instability
Acetyl Coenzyme A
Enzyme Activation
Salmonella enterica
Cell Aging
Protein S
Gene Silencing
Coenzyme A
Luciferases
Immunoblotting
NAD
Mass Spectrometry

ASJC Scopus subject areas

  • General

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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

Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine. / Starai, V. J.; Celic, I.; Cole, Robert N; Boeke, J. D.; Escalante-Semerena, J. C.

In: Science, Vol. 298, No. 5602, 20.12.2002, p. 2390-2392.

Research output: Contribution to journalArticle

Starai, VJ, Celic, I, Cole, RN, Boeke, JD & Escalante-Semerena, JC 2002, 'Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine', Science, vol. 298, no. 5602, pp. 2390-2392. https://doi.org/10.1126/science.1077650
Starai, V. J. ; Celic, I. ; Cole, Robert N ; Boeke, J. D. ; Escalante-Semerena, J. C. / Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine. In: Science. 2002 ; Vol. 298, No. 5602. pp. 2390-2392.
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