The X-linked IAP (XIAP) is an extremely powerful inhibitor of apoptosis. This is done through the binding to caspases directly. Similar to the functionality of NAIP, the BIR3 domain of XAIP binds to the carboxyl-terminal subunit of caspase-9. Between S1 and S1’ is where the catalysis occurs. In caspase-3 the ‘hook’ and ‘sinker’ attach. Both the BIR2 and BIR3 have a groove that is predominately negatively charged. This negative charge in BIR3 allows the attachment of the IAP-binding motif, causing enzymatic activity to be inhibited. When overexpressed, XAIP is able to block caspases extremely well and prevents cell death of sympathetic neurons when nerve growth factors are deprived.
The X-linked IAP (XIAP) is an extremely powerful inhibitor of apoptosis. This is done through the binding to caspases directly. Similar to the functionality of NAIP, the BIR3 domain of XIAP binds to the carboxyl-terminal subunit of caspase-9. Between S1 and S1’ is where the catalysis occurs. In caspase-3 the ‘hook’ and ‘sinker’ attach. Both the BIR2 and BIR3 have a groove that is predominately negatively charged. This negative charge in BIR3 allows the attachment of the IAP-binding motif, causing enzymatic activity to be inhibited. When overexpressed, XIAP is able to block caspases extremely well and prevents cell death of sympathetic neurons when nerve growth factors are deprived.
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