Sirtuin chemical mechanisms

Biochim Biophys Acta. 2010 Aug;1804(8):1591-603. doi: 10.1016/j.bbapap.2010.01.021. Epub 2010 Feb 2.

Abstract

Sirtuins are ancient proteins widely distributed in all lifeforms of earth. These proteins are universally able to bind NAD(+), and activate it to effect ADP-ribosylation of cellular nucleophiles. The most commonly observed sirtuin reaction is the ADP-ribosylation of acetyllysine, which leads to NAD(+)-dependent deacetylation. Other types of ADP-ribosylation have also been observed, including protein ADP-ribosylation, NAD(+) solvolysis and ADP-ribosyltransfer to 5,6-dimethylbenzimidazole, a reaction involved in eubacterial cobalamin biosynthesis. This review broadly surveys the chemistries and chemical mechanisms of these enzymes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylation
  • Adenosine Diphosphate Ribose / metabolism
  • Animals
  • Benzimidazoles / metabolism
  • Humans
  • Imidoesters / metabolism
  • Lysine / analogs & derivatives
  • Lysine / metabolism
  • Models, Biological
  • Molecular Structure
  • NAD / metabolism
  • Niacinamide / metabolism
  • Niacinamide / pharmacology
  • Plasmodium falciparum / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism
  • Sirtuins / antagonists & inhibitors
  • Sirtuins / chemistry
  • Sirtuins / metabolism*
  • Trypanosoma brucei brucei / metabolism

Substances

  • Benzimidazoles
  • Imidoesters
  • NAD
  • N(alpha)-acetyllysine
  • Adenosine Diphosphate Ribose
  • Niacinamide
  • 5,6-dimethylbenzimidazole
  • Sirtuins
  • Lysine