5LAI

Ligand-induced aziridine-formation at the yeast proteasomal subunit beta5 by sulfonate esters

5LAI の概要

• エントリーDOI: 10.2210/pdb5lai/pdb
• 関連するPDBエントリー: 4R17 5CZ4
• 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, fluorescent probes, binding analysis, umpolung, crosslink, hydrolase
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); 詳細
• 細胞内の位置: Cytoplasm: P23639 P22141 P30656 P23724 P30657 P38624 P23638 P40303 P32379 P40302 P21242 P21243 P25043 P25451
• タンパク質・核酸の鎖数: 28
• 化学式量合計: 731520.33

構造登録者

Groll, M.,Dubiella, C.,Cui, H. (登録日: 2016-06-14, 公開日: 2017-04-26, 最終更新日: 2025-10-01)

主引用文献

Dubiella, C.,Cui, H.,Groll, M.
Tunable Probes with Direct Fluorescence Signals for the Constitutive and Immunoproteasome.
Angew. Chem. Int. Ed. Engl., 55:13330-13334, 2016

PubMed Abstract: Electrophiles are commonly used for the inhibition of proteases. Notably, inhibitors of the proteasome, a central determinant of cellular survival and a target of several FDA-approved drugs, are mainly characterized by the reactivity of their electrophilic head groups. We aimed to tune the inhibitory strength of peptidic sulfonate esters by varying the leaving groups. Indeed, proteasome inhibition correlated well with the pK of the leaving group. The use of fluorophores as leaving groups enabled us to design probes that release a stoichiometric fluorescence signal upon reaction, thereby directly linking proteasome inactivation to the readout. This principle could be applicable to other sulfonyl fluoride based inhibitors and allows the design of sensitive probes for enzymatic studies.

PubMed: 27709817
DOI: 10.1002/anie.201605753

実験手法

X-RAY DIFFRACTION (2.5 Å)