6CKZ

Human caspase-3 in complex with Ac-DW3-KE

6CKZ の概要

• エントリーDOI: 10.2210/pdb6ckz/pdb
• 関連するBIRD辞書のPRD_ID: PRD_002449
• 分子名称: Caspase-3 subunit p17, Caspase-3 subunit p12, ACE-1MH-ASP-B3L-PHE-1U8, ... (4 entities in total)
• 機能のキーワード: caspase-3, inhibitor, apoptosis, hydrolase, 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: 3
• 化学式量合計: 33584.03

構造登録者

Solania, A.T.,Gonzalez-Paez, G.E.,Wolan, D.W. (登録日: 2018-03-01, 公開日: 2019-03-06, 最終更新日: 2023-11-15)

主引用文献

Solania, A.,Gonzalez-Paez, G.E.,Wolan, D.W.
Selective and Rapid Cell-Permeable Inhibitor of Human Caspase-3.
Acs Chem.Biol., 14:2463-2470, 2019

PubMed Abstract: Individual roles and overlapping functionalities of 12 human caspases during apoptosis and other cellular processes remain poorly resolved primarily due to a lack of chemical tools. Here we present a new selective caspase-3 inhibitor, termed Ac-ATS010-KE, with rapid and irreversible binding kinetics. Relative to previously designed caspase-3-selective molecules that have tremendously abated inhibitory rates and thus limited use in biological settings, the improved kinetics of Ac-ATS010-KE permits its use in a cell-based capacity. We demonstrate that Ac-ATS010-KE prevents apoptosis with comparable efficacy to the general caspase inhibitor Ac-DEVD-KE and surprisingly does so without side-chain methylation. This observation is in contrast to the well-established peptide modification strategy typically employed for improving cellular permeability. Ac-ATS010-KE protects against extrinsic apoptosis, which demonstrates the utility of a thiophene carboxylate leaving group in biological settings, challenges the requisite neutralization of free carboxylic acids to improve cell permeability, and provides a tool-like compound to interrogate the role of caspase-3 in a variety of cellular processes.

PubMed: 31334631
DOI: 10.1021/acschembio.9b00564

実験手法

X-RAY DIFFRACTION (1.5 Å)