1GQF

Crystal structure of human procaspase-7

1GQF の概要

• エントリーDOI: 10.2210/pdb1gqf/pdb
• 関連するPDBエントリー: 1F1J 1I4O
• 分子名称: Caspase-7, SULFATE ION (3 entities in total)
• 機能のキーワード: caspase-7, hydrolase, apoptosis, zymogen
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61046.98

構造登録者

Riedl, S.,Bode, W.,Fuentes-Prior, P. (登録日: 2001-11-23, 公開日: 2002-01-04, 最終更新日: 2023-12-13)

主引用文献

Riedl, S.J.,Fuentes-Prior, P.,Renatus, M.,Kairies, N.,Krapp, S.,Huber, R.,Salvesen, G.S.,Bode, W.
Structural basis for the activation of human procaspase-7.
Proc. Natl. Acad. Sci. U.S.A., 98:14790-14795, 2001

PubMed Abstract: Caspases form a family of proteinases required for the initiation and execution phases of apoptosis. Distinct proapoptotic stimuli lead to activation of the initiator caspases-8 and -9, which in turn activate the common executioner caspases-3 and -7 by proteolytic cleavage. Whereas crystal structures of several active caspases have been reported, no three-dimensional structure of an uncleaved caspase zymogen is available so far. We have determined the 2.9-A crystal structure of recombinant human C285A procaspase-7 and have elucidated the activation mechanism of caspases. The overall fold of the homodimeric procaspase-7 resembles that of the active tetrameric caspase-7. Each monomer is organized in two structured subdomains connected by partially flexible linkers, which asymmetrically occupy and block the central cavity, a typical feature of active caspases. This blockage is incompatible with a functional substrate binding site/active site. After proteolytic cleavage within the flexible linkers, the newly formed chain termini leave the cavity and fold outward to form stable structures. These conformational changes are associated with the formation of an intact active-site cleft. Therefore, this mechanism represents a formerly unknown type of proteinase zymogen activation.

PubMed: 11752425
DOI: 10.1073/pnas.221580098

実験手法

X-RAY DIFFRACTION (2.9 Å)