4NO1

yCP in complex with Z-Leu-Leu-Leu-B(OH)2

4NO1 の概要

• エントリーDOI: 10.2210/pdb4no1/pdb
• 関連するPDBエントリー: 1RYP 4NNN 4NNW 4NO6 4NO8 4NO9
• 関連するBIRD辞書のPRD_ID: PRD_000909
• 分子名称: Proteasome subunit alpha type-2, Proteasome subunit beta type-4, Proteasome subunit beta type-5, ... (17 entities in total)
• 機能のキーワード: proteasome, peptide electrophile, binding analysis, irreversible inhibitor, boronic acid, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Saccharomyces cerevisiae S288c (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 28
• 化学式量合計: 732228.07

構造登録者

Stein, M.L.,Cui, H.,Beck, P.,Dubiella, C.,Voss, C.,Krueger, A.,Schmidt, B.,Groll, M. (登録日: 2013-11-19, 公開日: 2014-02-12, 最終更新日: 2023-09-20)

主引用文献

Stein, M.L.,Cui, H.,Beck, P.,Dubiella, C.,Voss, C.,Kruger, A.,Schmidt, B.,Groll, M.
Systematic Comparison of Peptidic Proteasome Inhibitors Highlights the alpha-Ketoamide Electrophile as an Auspicious Reversible Lead Motif.
Angew.Chem.Int.Ed.Engl., 53:1679-1683, 2014

PubMed Abstract: The ubiquitin-proteasome system (UPS) has been successfully targeted by both academia and the pharmaceutical industry for oncological and immunological applications. Typical proteasome inhibitors are based on a peptidic backbone endowed with an electrophilic C-terminus by which they react with the active proteolytic sites. Although the peptide moiety has attracted much attention in terms of subunit selectivity, the target specificity and biological stability of the compounds are largely determined by the reactive warheads. In this study, we have carried out a systematic investigation of described electrophiles by a combination of in vitro, in vivo, and structural methods in order to disclose the implications of altered functionality and chemical reactivity. Thereby, we were able to introduce and characterize the class of α-ketoamides as the most potent reversible inhibitors with possible applications for the therapy of solid tumors as well as autoimmune disorders.

PubMed: 24403024
DOI: 10.1002/anie.201308984

実験手法

X-RAY DIFFRACTION (2.5 Å)