Sirtuins: NAD+-dependent deacetylase mechanism and regulation

Anthony A. Sauve, Dou Yeon Youn

Research output: Contribution to journalReview article

50 Citations (Scopus)

Abstract

Sirtuins are NAD+-dependent deacetylases involved in chemical reversal of acetyllysine modifications of cellular proteins. Deacetylation catalyzed by sirtuins is implicated in regulating diverse biological processes, including energy homeostasis. The mechanism of NAD+-dependent deacetylation is proposed to occur via an ADPR-peptidyl-imidate intermediate, resulting from reaction of NAD+ and an acetyllysine residue. This mechanism enables sirtuins to respond dynamically to intracellular fluctuations of NAD+ and nicotinamide. Chemical probes such as nicotinamide antagonists and thioacetyl compounds provide key support for the imidate mechanism of sirtuin deacetylation catalysis. Novel new directions include chemical probes to study sirtuins in cells, and the discovery of novel post-translational modifications besides acetyl, such as succinyl and malonyl, that are regulated by sirtuins.

Original languageEnglish (US)
Pages (from-to)535-543
Number of pages9
JournalCurrent Opinion in Chemical Biology
Volume16
Issue number5-6
DOIs
StatePublished - Dec 1 2012
Externally publishedYes

Fingerprint

Sirtuins
NAD
Imidoesters
Niacinamide
Biological Phenomena
Post Translational Protein Processing
Catalysis
Catalyst supports
Homeostasis
Proteins

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry

Cite this

Sirtuins : NAD+-dependent deacetylase mechanism and regulation. / Sauve, Anthony A.; Youn, Dou Yeon.

In: Current Opinion in Chemical Biology, Vol. 16, No. 5-6, 01.12.2012, p. 535-543.

Research output: Contribution to journalReview article

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