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.
Sauve
Anthony A
AA
Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10065, USA. aas2004@med.cornell.edu
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