4FDL

Crystal structure of Caspase-7

4FDL の概要

• エントリーDOI: 10.2210/pdb4fdl/pdb
• 関連するPDBエントリー: 4FEA
• 分子名称: Caspase-7 (2 entities in total)
• 機能のキーワード: cysteine protease, central cavity, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P55210
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69132.20

構造登録者

Kabaleeswaran, V. (登録日: 2012-05-28, 公開日: 2012-08-01, 最終更新日: 2023-09-13)

主引用文献

Feldman, T.,Kabaleeswaran, V.,Jang, S.B.,Antczak, C.,Djaballah, H.,Wu, H.,Jiang, X.
A class of allosteric caspase inhibitors identified by high-throughput screening.
Mol.Cell, 47:585-595, 2012

PubMed Abstract: Caspase inhibition is a promising approach for treating multiple diseases. Using a reconstituted assay and high-throughput screening, we identified a group of nonpeptide caspase inhibitors. These inhibitors share common chemical scaffolds, suggesting the same mechanism of action. They can inhibit apoptosis in various cell types induced by multiple stimuli; they can also inhibit caspase-1-mediated interleukin generation in macrophages, indicating potential anti-inflammatory application. While these compounds inhibit all the tested caspases, kinetic analysis indicates they do not compete for the catalytic sites of the enzymes. The cocrystal structure of one of these compounds with caspase-7 reveals that it binds to the dimerization interface of the caspase, another common structural element shared by all active caspases. Consistently, biochemical analysis demonstrates that the compound abates caspase-8 dimerization. Based on these kinetic, biochemical, and structural analyses, we suggest that these compounds are allosteric caspase inhibitors that function through binding to the dimerization interface of caspases.

PubMed: 22795132
DOI: 10.1016/j.molcel.2012.06.007

実験手法

X-RAY DIFFRACTION (2.801 Å)