(A) Combined sequence logo for substrate preferences in caspases (left) and substrate preferences for Group I–III caspases (right). (B) Comparison of sequences for HsCasp-3, DrCasp-3a and DrCasp-3b. Common position numbering scheme and secondary structural elements are shown above each line, and actual position numbers are shown at the end of each row. Amino acids marked in orange show the charged amino acids in panel (D). Panels (C,D). The charged amino acid network in HsCasp-6 (PDB ID 3S70) (C) is incomplete in HsCasp-3 (PDB ID 2J30) (D). The red box indicates the start of the common position (CP) sites. In panels (C,D), red spheres represent water molecules, and black dashed lines represent hydrogen bonds. Inhibitors are shown as purple (VEID, panel (C)) or green (DEVD, panel (D)). Residues corresponding to P4, P3, P2 and P1 of the inhibitor are labeled, and the corresponding binding pockets for P4 (called S4) and for P3 (called S3) are labeled in red.