5XVE

Crystal structure of human USP2 C276S mutant in complex with ubiquitin

Summary for 5XVE

• Entry DOI: 10.2210/pdb5xve/pdb
• Descriptor: Ubiquitin carboxyl-terminal hydrolase 2, Ubiquitin-40S ribosomal protein S27a, ZINC ION, ... (4 entities in total)
• Functional Keywords: ubiquitin specific protease for anticancer target, hydrolase
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm . Isoform 4: Nucleus : O75604; Ubiquitin: Cytoplasm : P62992
• Total number of polymer chains: 2
• Total formula weight: 49835.83

Authors

Chou, C.Y.,Tang, H.C. (deposition date: 2017-06-27, release date: 2018-02-28, Last modification date: 2023-11-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.24 Å)