Sirtuins Caught in the Act Brian C. Smith, John M. Denu  Structure  Volume 14, Issue 8, Pages 1207-1208 (August 2006) DOI: 10.1016/j.str.2006.07.004 Copyright © 2006 Elsevier Ltd Terms and Conditions

Figure 1 Proposed Mechanism of Sir2 Protein Deacetylases Acetyl-lysine substrate and nicotinamide adenine dinucleotide bind to Sir2 deacetylases to form a ternary complex. After binding, the reaction proceeds through either an SN1- or SN2-like mechanism to release nicotinamide and produce the O-alkylamidate intermediate resulting from acetyl-lysine carbonyl oxygen attack at the 1′-carbon of the nicotinamide ribose. The O-alkylamidate intermediate is then hydrolyzed through multiple steps to form a product complex from which deacetylated-lysine product and O-acetyl-ADP-ribose are released. The coordinates used to depict the structures in the figure were provided by Kevin Hoff and Cynthia Wolberger (Hoff et al., 2006). Structure 2006 14, 1207-1208DOI: (10.1016/j.str.2006.07.004) Copyright © 2006 Elsevier Ltd Terms and Conditions