5XU8
Crystal structure of human USP2 in complex with ubiquitin and 6-thioguanine
Summary for 5XU8
| Entry DOI | 10.2210/pdb5xu8/pdb |
| Descriptor | Ubiquitin carboxyl-terminal hydrolase 2, Ubiquitin-40S ribosomal protein S27a, 2-amino-1,9-dihydro-6H-purine-6-thione, ... (7 entities in total) |
| Functional Keywords | ternary complex, esi complex, 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 | 50311.30 |
| Authors | Chou, C.Y.,Chuang, S.J. (deposition date: 2017-06-22, release date: 2018-02-28, Last modification date: 2024-11-13) |
| 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 Cited by 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: 29449607DOI: 10.1038/s41598-018-21476-w PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.81 Å) |
Structure validation
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