Volume 104, Issue 6, Pages 805-808 (March 2001) Cell Death Inhibition  Lakshmi Goyal  Cell  Volume 104, Issue 6, Pages 805-808 (March 2001) DOI: 10.1016/S0092-8674(01)00276-8

Figure 1 Mechanisms of Caspase Inhibition by IAPs (A) As revealed by the structures published earlier this month in Cell (Chai et al., 2001; Huang et al., 2001; Riedl et al., 2001), the linker region N-terminal to the BIR2 domain of XIAP is a major structural determinant in binding to the active form of caspase-3 and -7. This complex may be destabilized by the interaction of Smac/DIABLO with BIR2 due to a conformation change. Release of IAP complexed with Smac/DIABLO would relieve the inhibition on the caspase and the active caspase is then free to induce cell death. (B) Caspase-9 inhibition by the BIR3 domain of XIAP requires the initial processing of the pro enzyme to expose the IAP binding motif at the N terminus of the small subunit (Srinivasula et al., 2001). Once exposed BIR3 can bind to the IAP binding motif of caspase-9 and hinder the entry of substrate to the active site of the enzyme. Smac/DIABLO competes with cleaved caspase-9 for binding to BIR3 and the binding partner then determines if the cell undergoes apoptosis Cell 2001 104, 805-808DOI: (10.1016/S0092-8674(01)00276-8)