XIAP binds CASP3

Stable Identifier
R-HSA-9627104
Type
Reaction [binding]
Species
Homo sapiens
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X‑linked inhibitor of apoptosis protein (XIAP) suppresses cell death by inhibiting the catalytic activity of caspases (Deveraux QL et al. 1997; Paulsen M et al. 2008). XIAP consists of three bacculoviral inhibitory repeat (BIR) domains and a C‑terminal ring finger. Biochemical and structural analyses revealed that the linker connecting BIR1 to BIR2 inhibits executioner caspase‑3 and ‑7 by positioning itself at the active site (Sun C et al. 1999; Riedl SJ et al. 2001; Huang Y et al. 2001; Chai J et al. 2001). Formation of a complex between caspase‑3 or caspase‑7 and the XIAP BIR2‑linker region appears to be driven by interactions between XIAP's Leu141 and Val146 and a hydrophobic site present on both caspases. This hydrophobic site is not found in caspase‑8 or caspase‑9, perhaps explaining the binding specificity of XIAP (Riedl SJ et al. 2001). BIR2 domain of XIAP may also contribute to inhibition of executioner caspases by interacting with additional sites on the enzymes (Scott FL et al. 2005; Abhari BA & Davoodi J 2008).

Literature References
PubMed ID Title Journal Year
11257231 Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain

Huang, Y, Park, YC, Rich, RL, Segal, D, Myszka, DG, Wu, H

Cell 2001
15650747 XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs

Scott, FL, Denault, JB, Riedl, SJ, Shin, H, Renatus, M, Salvesen, GS

EMBO J. 2005
11230124 Recruitment, activation and retention of caspases-9 and -3 by Apaf-1 apoptosome and associated XIAP complexes

Bratton, SB, Walker, G, Srinivasula, SM, Sun, XM, Butterworth, M, Alnemri, ES, Cohen, GM

EMBO J. 2001
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