5XVE

Crystal structure of human USP2 C276S mutant in complex with ubiquitin

5XVE の概要

• エントリーDOI: 10.2210/pdb5xve/pdb
• 分子名称: Ubiquitin carboxyl-terminal hydrolase 2, Ubiquitin-40S ribosomal protein S27a, ZINC ION, ... (4 entities in total)
• 機能のキーワード: ubiquitin specific protease for anticancer target, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm . Isoform 4: Nucleus : O75604; Ubiquitin: Cytoplasm : P62992
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49835.83

構造登録者

Chou, C.Y.,Tang, H.C. (登録日: 2017-06-27, 公開日: 2018-02-28, 最終更新日: 2023-11-22)

主引用文献

Chuang, S.J.,Cheng, S.C.,Tang, H.C.,Sun, C.Y.,Chou, C.Y.
6-Thioguanine is a noncompetitive and slow binding inhibitor of human deubiquitinating protease USP2
Sci Rep, 8:3102-3102, 2018

PubMed Abstract: Ubiquitin-specific protease 2 (USP2) belongs to the family of deubiquitinases that can rescue protein targets from proteasomal degradation by reversing their ubiquitination. In various cancers, including prostate cancer and ovarian carcinoma, upregulation of USP2 leads to an increase in the levels of deubiquitinated substrates such as fatty acid synthase, MDM2, cyclin D1 and Aurora-A. USP2 thus plays a critical role in tumor cells' survival and therefore represents a therapeutic target. Here a leukemia drug, 6-thioguanine, was found to be a potent inhibitor of USP2. Enzyme-kinetic and X-ray crystallographic data suggest that 6-thioguanine displays a noncompetitive and slow-binding inhibitory mechanism against USP2. Our study provides a clear rationale for the clinical evaluation of 6-thioguanine for USP2-upregulated cancers.

PubMed: 29449607
DOI: 10.1038/s41598-018-21476-w

実験手法

X-RAY DIFFRACTION (1.24 Å)