In A and B, the ADPr-SIRT2 structure is shown in cyan, zinc is colored orange, ADP-ribose is colored yellow, and residues photolabeled by AziPm are shown as red sticks. The propofol binding cavity is filled with the black surface representation. A, the C-pocket residues of SIRT2 were aligned to the C-pocket residues of Sir2Tm (PDB code 1YC5). The alignment root mean square was 0.75 Å, and the Sir2Tm C-pocket residues are traced in the transparent magenta. In 1YC5, Sir2Tm is bound to nicotinamide, and the position of this inhibitor, which binds to a separate site than propofol, is shown as green sticks. B, the C-pocket residues of SIRT2 were aligned to those of SIRT3 (PDB code 4BV3). The alignment root mean square was 0.26 Å, and the SIRT3 C-pocket residues are traced in the transparent magenta. In 4BV3, SIRT3 is bound to the inhibitor Ex-527, which binds to the same site as nicotinamide and is shown as green sticks.