3EDR

The crystal structure of caspase-7 in complex with Acetyl-LDESD-CHO

3EDR の概要

• エントリーDOI: 10.2210/pdb3edr/pdb
• 関連するPDBエントリー: 3EDQ
• 関連するBIRD辞書のPRD_ID: PRD_000241
• 分子名称: Caspase-7, Inhibitor Ac-ldesd-cho peptide, ... (4 entities in total)
• 機能のキーワード: caspase, peptide inhibitor, apoptosis, thiol protease, 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: P55210 P55210
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 63014.11

構造登録者

Agniswamy, J. (登録日: 2008-09-03, 公開日: 2008-10-28, 最終更新日: 2023-11-15)

主引用文献

Fu, G.,Chumanevich, A.A.,Agniswamy, J.,Fang, B.,Harrison, R.W.,Weber, I.T.
Structural basis for executioner caspase recognition of P5 position in substrates.
Apoptosis, 13:1291-1302, 2008

PubMed Abstract: Caspase-3, -6 and -7 cleave many proteins at specific sites to induce apoptosis. Their recognition of the P5 position in substrates has been investigated by kinetics, modeling and crystallography. Caspase-3 and -6 recognize P5 in pentapeptides as shown by enzyme activity data and interactions observed in the crystal structure of caspase-3/LDESD and in a model for caspase-6. In caspase-3 the P5 main-chain was anchored by interactions with Ser209 in loop-3 and the P5 Leu side-chain interacted with Phe250 and Phe252 in loop-4 consistent with 50% increased hydrolysis of LDEVD relative to DEVD. Caspase-6 formed similar interactions and showed a preference for polar P5 in QDEVD likely due to interactions with polar Lys265 and hydrophobic Phe263 in loop-4. Caspase-7 exhibited no preference for P5 residue in agreement with the absence of P5 interactions in the caspase-7/LDESD crystal structure. Initiator caspase-8, with Pro in the P5-anchoring position and no loop-4, had only 20% activity on tested pentapeptides relative to DEVD. Therefore, caspases-3 and -6 bind P5 using critical loop-3 anchoring Ser/Thr and loop-4 side-chain interactions, while caspase-7 and -8 lack P5-binding residues.

PubMed: 18780184
DOI: 10.1007/s10495-008-0259-9

実験手法

X-RAY DIFFRACTION (2.45 Å)