1JXQ

Structure of cleaved, CARD domain deleted Caspase-9

1JXQ の概要

• エントリーDOI: 10.2210/pdb1jxq/pdb
• 関連するPDBエントリー: 3YGS
• 分子名称: Caspase-9, benzoxycarbonyl-Val-Ala-Asp-fluoromethyl ketone Inhibitor (3 entities in total)
• 機能のキーワード: protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 126794.62

構造登録者

Renatus, M.,Stennicke, H.R.,Scott, F.L.,Liddington, R.C.,Salvesen, G.S. (登録日: 2001-09-08, 公開日: 2001-12-12, 最終更新日: 2024-11-13)

主引用文献

Renatus, M.,Stennicke, H.R.,Scott, F.L.,Liddington, R.C.,Salvesen, G.S.
Dimer formation drives the activation of the cell death protease caspase 9.
Proc.Natl.Acad.Sci.USA, 98:14250-14255, 2001

PubMed Abstract: A critical step in the induction of apoptosis is the activation of the apoptotic initiator caspase 9. We show that at its normal physiological concentration, caspase 9 is primarily an inactive monomer (zymogen), and that activity is associated with a dimeric species. At the high concentrations used for crystal formation, caspase 9 is dimeric, and the structure reveals two very different active-site conformations within each dimer. One site closely resembles the catalytically competent sites of other caspases, whereas in the second, expulsion of the "activation loop" disrupts the catalytic machinery. We propose that the inactive domain resembles monomeric caspase 9. Activation is induced by dimerization, with interactions at the dimer interface promoting reorientation of the activation loop. These observations support a model in which recruitment by Apaf-1 creates high local concentrations of caspase 9 to provide a pathway for dimer-induced activation.

PubMed: 11734640
DOI: 10.1073/pnas.231465798

実験手法

X-RAY DIFFRACTION (2.8 Å)