Smac/DIABLO displaces caspase-9 from BIR3 of XIAP. (A) Crystal structure of processed caspase-9 bound to BIR3 of XIAP. The purple peptide represents the first 4 amino acids that contact XIAP, with the amino terminus near the orange residue of XIAP. Coordinates were obtained from Brookhaven Protein Databank file 1NW9 (82). (B) NMR structure of the Smac/DIABLO IBM (purple peptide with the amino terminus near the orange residue of XIAP) bound to the same groove on BIR3 of XIAP that binds caspase-9, thus abrogating the ability of XIAP to block caspase-9 activity. Coordinates were obtained from Brookhaven Protein Databank file 1G3F (83). The 4 residues displayed in van der Waals radii spacefill on XIAP BIR3 are Gly306 (red), Leu307 (green), Trp310 (yellow), and Glu314 (orange). These 4 residues are critical in forming the Smac/DIABLO–binding groove on XIAP BIR3 (84). Images were created using Protein Explorer (85, 86).