The Substrate Specificity of Sirtuins

Annu Rev Biochem. 2016 Jun 2:85:405-29. doi: 10.1146/annurev-biochem-060815-014537. Epub 2016 Apr 18.

Abstract

Sirtuins are NAD(+)-dependent enzymes universally present in all organisms, where they play central roles in regulating numerous biological processes. Although early studies showed that sirtuins deacetylated lysines in a reaction that consumes NAD(+), more recent studies have revealed that these enzymes can remove a variety of acyl-lysine modifications. The specificities for varied acyl modifications may thus underlie the distinct roles of the different sirtuins within a given organism. This review summarizes the structure, chemistry, and substrate specificity of sirtuins with a focus on how different sirtuins recognize distinct substrates and thus carry out specific functions.

Keywords: ADP-ribosylation; deacylation; myristoylation; palmitoylation; succinylation.

Publication types

  • Review

MeSH terms

  • Acylation
  • Gene Expression
  • Histones / chemistry*
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Hydrolysis
  • Kinetics
  • Lipoylation
  • Models, Molecular
  • Myristic Acid / chemistry
  • Myristic Acid / metabolism
  • NAD / chemistry*
  • NAD / metabolism
  • Plasmodium falciparum / chemistry
  • Plasmodium falciparum / enzymology
  • Protein Processing, Post-Translational*
  • Protein Structure, Secondary
  • Sirtuins / chemistry*
  • Sirtuins / genetics
  • Sirtuins / metabolism
  • Substrate Specificity
  • Succinic Acid / chemistry
  • Succinic Acid / metabolism
  • Thermotoga maritima / chemistry
  • Thermotoga maritima / enzymology

Substances

  • Histones
  • Myristic Acid
  • NAD
  • Succinic Acid
  • Sirtuins