Sirtuin enzymatic deacylation of substrate. (A) Nicotinamide cleavage.
Nicotinamide adenine dinucleotide (NAD+) is shown in the purple and
green pockets of the representative SIRT enzyme. Acylated lysine protein
substrate is highlighted in the blue pocket. (B,C) Formation of the
alpha-1’-O-alkylamidate intermediate. Nicotinamide is shown in the purple
pocket, the alpha-1’-O-alkylamidate intermediate in the blue and green
pockets, and the SIRT catalytic histidine in the yellow pocket. (D) Deacylation
of lysine. The reaction yields deacylated lysine (blue pocket), nicotinamide
(purple pocket), and 2’-O-acetyl-adenosine diphosphate ribose (green
pocket).