Sirtuin chemical mechanisms.
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.
Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10065, USA. aas2004@med.cornell.edu
Anthony A
AA
Sauve
D000107:Acetylation; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism; D006801:Humans; D007096:Imidoesters / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008954:Models, Biological; D015394:Molecular Structure; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000378:metabolism / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000378:metabolism
D001562:Benzimidazoles; D007096:Imidoesters; D009243:NAD; C002315:N(alpha)-acetyllysine; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; C015158:5,6-dimethylbenzimidazole; D037761:Sirtuins; D008239:Lysine