3ITN

Crystal structure of Pseudo-activated Procaspase-3

3ITN の概要

• エントリーDOI: 10.2210/pdb3itn/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000238
• 分子名称: Caspase-3, ACETYL-ASP-GLU-VAL-ASP-CHLOROMETHYL KETONE inhibitor (3 entities in total)
• 機能のキーワード: caspase-3, apoptosis, hydrolase, phosphoprotein, protease, s-nitrosylation, thiol protease, zymogen, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P42574
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29168.53

構造登録者

Walters, J.,Pop, C.,Scott, F.L.,Drag, M.,Swartz, P.D.,Mattos, C.,Salvesen, G.S.,Clark, A.C. (登録日: 2009-08-28, 公開日: 2010-03-02, 最終更新日: 2024-11-20)

主引用文献

Walters, J.,Pop, C.,Scott, F.L.,Drag, M.,Swartz, P.,Mattos, C.,Salvesen, G.S.,Clark, A.C.
A constitutively active and uninhibitable caspase-3 zymogen efficiently induces apoptosis.
Biochem.J., 424:335-345, 2009

PubMed Abstract: The caspase-3 zymogen has essentially zero activity until it is cleaved by initiator caspases during apoptosis. However, a mutation of V266E in the dimer interface activates the protease in the absence of chain cleavage. We show that low concentrations of the pseudo-activated procaspase-3 kill mammalian cells rapidly and, importantly, this protein is not cleaved nor is it inhibited efficiently by the endogenous regulator XIAP (X-linked inhibitor of apoptosis). The 1.63 A (1 A = 0.1 nm) structure of the variant demonstrates that the mutation is accommodated at the dimer interface to generate an enzyme with substantially the same activity and specificity as wild-type caspase-3. Structural modelling predicts that the interface mutation prevents the intersubunit linker from binding in the dimer interface, allowing the active sites to form in the procaspase in the absence of cleavage. The direct activation of procaspase-3 through a conformational switch rather than by chain cleavage may lead to novel therapeutic strategies for inducing cell death.

PubMed: 19788411
DOI: 10.1042/BJ20090825

実験手法

X-RAY DIFFRACTION (1.63 Å)