4PS0

Caspase-8 specific unnatural amino acid peptides

4PS0 の概要

• エントリーDOI: 10.2210/pdb4ps0/pdb
• 関連するPDBエントリー: 4JJ7 4JJ8 4JJE 4PRY 4PRZ 4PS1
• 分子名称: Caspase-3, (BAL)LQ(HYP)(1U8) PEPTIDE (3 entities in total)
• 機能のキーワード: protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P42574
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 66853.72

構造登録者

Wolan, D.W.,Vickers, C.J.,Gonzalez-Paez, G.E. (登録日: 2014-03-06, 公開日: 2015-01-21, 最終更新日: 2024-04-03)

主引用文献

Vickers, C.J.,Gonzalez-Paez, G.E.,Litwin, K.M.,Umotoy, J.C.,Coutsias, E.A.,Wolan, D.W.
Selective inhibition of initiator versus executioner caspases using small peptides containing unnatural amino acids.
Acs Chem.Biol., 9:2194-2198, 2014

PubMed Abstract: Caspases are fundamental to many essential biological processes, including apoptosis, differentiation, and inflammation. Unregulated caspase activity is also implicated in the development and progression of several diseases, such as cancer, neurodegenerative disorders, and sepsis. Unfortunately, it is difficult to determine exactly which caspase(s) of the 11 isoforms that humans express is responsible for specific biological functions. This lack of resolution is primarily due to highly homologous active sites and overlapping substrates. Currently available peptide-based inhibitors and probes are based on specificity garnered from peptide substrate libraries. For example, the canonical tetrapeptide LETD was discovered as the canonical sequence that is optimally recognized by caspase-8; however, LETD-based inhibitors and substrates promiscuously bind to other isoforms with equal affinity, including caspases-3, -6, and -9. In order to mitigate this problem, we report the identification of a new series of compounds that are >100-fold selective for inhibiting the initiator caspases-8 and -9 over the executioner caspases-3, -6, and -7.

PubMed: 25079698
DOI: 10.1021/cb5004256

実験手法

X-RAY DIFFRACTION (1.63 Å)