2P2C

Inhibition of caspase-2 by a designed ankyrin repeat protein (DARPin)

2P2C の概要

• エントリーDOI: 10.2210/pdb2p2c/pdb
• 関連するPDBエントリー: 1MJO 1PYO
• 分子名称: Caspase-2, ... (4 entities in total)
• 機能のキーワード: apoptosis, caspase, caspase-2, inhibition, protein design, protein libraries, designed ankyrin repeat proteins, ribosome display, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 297019.76

構造登録者

Roschitzki Voser, H.,Briand, C.,Capitani, G.,Gruetter, M.G. (登録日: 2007-03-07, 公開日: 2007-05-22, 最終更新日: 2024-10-16)

主引用文献

Schweizer, A.,Roschitzki-Voser, H.,Amstutz, P.,Briand, C.,Gulotti-Georgieva, M.,Prenosil, E.,Binz, H.K.,Capitani, G.,Baici, A.,Pluckthun, A.,Grutter, M.G.
Inhibition of Caspase-2 by a Designed Ankyrin Repeat Protein: Specificity, Structure, and Inhibition Mechanism.
Structure, 15:625-636, 2007

PubMed Abstract: Specific and potent caspase inhibitors are indispensable for the dissection of the intricate pathways leading to apoptosis. We selected a designed ankyrin repeat protein (DARPin) from a combinatorial library that inhibits caspase-2 in vitro with a subnanomolar inhibition constant and, in contrast to the peptidic caspase inhibitors, with very high specificity for this particular caspase. The crystal structure of this inhibitor (AR_F8) in complex with caspase-2 reveals the molecular basis for the specificity and, together with kinetic analyses, the allosteric mechanism of inhibition. The structure also shows a conformation of the active site that can be exploited for the design of inhibitory compounds. AR_F8 is a specific inhibitor of an initiator caspase and has the potential to help identify the function of caspase-2 in the complex biological apoptotic signaling network.

PubMed: 17502107
DOI: 10.1016/j.str.2007.03.014

実験手法

X-RAY DIFFRACTION (3.24 Å)