Figure 2

Three-dimensional high-resolution crystal structures of four sirtuin proteins. The zinc-binding module is shown at the top left in each panel, the helical modules of the small domain are lighter and at the top right, and the large Rossmann-fold domain is in the lower half. Each α helix and β strand is labeled to facilitate comparisons. (a) Sir2-Af1 complexed with NAD (in stick representation; PDB accession number: 1ICI) [20]. (b) Sir2-Af2 complexed with acetylated p53 peptide (in stick notation, with acetyl-lysine darker). Two β strands (β10 and β11) are shown that might mediate the binding of the substrate peptide (PDB accession number: IMA3) [21]. An acetylated peptide, such as p53, may be bound through the formation of an enzyme-substrate β sheet, in which the substrate β strand is sandwiched between the β11 strand within the Rossmann fold and a β10 strand within the FGE loop, named for its highly conserved FGExL motif [21]. (c) Human Sirt2 (catalytic core; PDB accession number: 1J8F) [18]. (d) Full-length yeast Hst2p with the carboxy-terminal α14 helix interacting with the NAD-binding pocket (PDB accession number: 1Q14) [19]. Structural coordinates were taken from the Protein Data Bank and models were drawn with PYMOL [77].