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Figure 1.
Figure 1. Sirtuin Deacetylation Reaction Mechanism
(A
and B) (A) In the first step of the Sir2 deacetylation reaction
(I), the ADP-ribose moiety of NAD^+ is transferred to
acetyl-lysine, generating the O-alkylamidate intermediate. In
this step (I), the nicotinamide-N-ribose bond is broken to
generate free nicotinamide. Next, the N-ribose 2′OH group
attacks the O-alkylamidate intermediate, generating a 1′,2′
bicyclic species (II). Subsequent hydrolysis of the 1′,2′
bicyclic species yields deacetylated lysine and
2′O-acetyl-ADP-ribose (III). The structure of the DADMe-NAD^+
analog, which represents a dissociated NAD^+ species, is
depicted in (B).
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