9R1P
Crystal structure of STUB1 complexed with a compound molecule
This is a non-PDB format compatible entry.
Summary for 9R1P
| Entry DOI | 10.2210/pdb9r1p/pdb |
| Descriptor | E3 ubiquitin-protein ligase CHIP, 1-[3-[1-methyl-4-(pyridin-3-ylmethylamino)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[3-(trifluoromethyl)phenyl]thiourea (3 entities in total) |
| Functional Keywords | stip1 homology and u-box containing protein 1, e3 ubiquitin ligase, cell cycle |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 16327.42 |
| Authors | |
| Primary citation | Chu, Y.,Chen, S.,Yang, M.,Chen, Y.,Fang, H.,Huang, P.,Xie, Y.,Sun, C.,Chen, Y.,Zhang, B.,Li, L.,Mu, H.,Song, D.,Cheng, W.,Wang, C.,Jiang, W.,Xu, X.,He, Z.,Chen, S.,Liu, M.,Ma, J.,Yang, M.,Cao, J.,Gao, J.,Shen, J.,Zhang, L.,Bai, Y.,Liu, Z.,Chen, J.,Dai, S.,Zeng, Y.A.,Zhao, Y.,Zhou, H.,Chen, C.,Ru, H.,Tan, L.,Chi, X.,Wang, F.,Gao, D.,Lin, M.,Deng, X.,Jiang, H. A rapid imaging-based screen for induced-proximity degraders identifies a potent degrader of oncoprotein SKP2. Nat.Biotechnol., 2025 Cited by PubMed Abstract: Targeted protein degraders hold potential as therapeutic agents to target conventionally 'undruggable' proteins. Here, we develop a high-throughput screen, DEath FUSion Escaper (DEFUSE), to identify small-molecule protein degraders. By conjugating the protein of interest to a fast-acting triggerable death protein, this approach translates target protein degradation into a cell survival phenotype to illustrate the presence of degraders. Using this method, we discovered a small molecule (SKPer1) that triggers degradation of the oncoprotein SKP2 and specifically kills SKP2-expressing cancer cells. Mechanistically, SKPer1 acts as an induced-proximity degrader by inducing interaction between SKP2 and an E3 ligase, STUB1, resulting in SKP2 ubiquitination and degradation. SKPer1 exhibits substantial tumour suppression with good safety profiles in vivo. We further show that a sequence of ten amino acids from SKP2 can serve as a versatile degradation tag. PubMed: 40931108DOI: 10.1038/s41587-025-02793-8 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.29 Å) |
Structure validation
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