8ITP

Crystal structure of USP47 catalytic domain complex with ubiquitin

Summary for 8ITP

• Entry DOI: 10.2210/pdb8itp/pdb
• Descriptor: Ubiquitin, Ubiquitin carboxyl-terminal hydrolase 47, ZINC ION (3 entities in total)
• Functional Keywords: ubiquitin specific protease, hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 132420.25

Authors

Kim, E.E.,Shin, S.C. (deposition date: 2023-03-22, release date: 2024-03-27, Last modification date: 2024-05-08)

Primary citation

Shin, S.C.,Park, J.,Kim, K.H.,Yoon, J.M.,Cho, J.,Ha, B.H.,Oh, Y.,Choo, H.,Song, E.J.,Kim, E.E.
Structural and functional characterization of USP47 reveals a hot spot for inhibitor design.
Commun Biol, 6:970-970, 2023

PubMed Abstract: USP47 is widely involved in tumor development, metastasis, and other processes while performing a more regulatory role in inflammatory responses, myocardial infarction, and neuronal development. In this study, we investigate the functional and biochemical properties of USP47, whereby depleting USP47 inhibited cancer cell growth in a p53-dependent manner-a phenomenon that enhances during the simultaneous knockdown of USP7. Full-length USP47 shows higher deubiquitinase activity than the catalytic domain. The crystal structures of the catalytic domain, in its free and ubiquitin-bound states, reveal that the misaligned catalytic triads, ultimately, become aligned upon ubiquitin-binding, similar to USP7, thereby becoming ready for catalysis. Yet, the composition and lengths of BL1, BL2, and BL3 of USP47 differ from those for USP7, and they contribute to the observed selectivity. Our study provides molecular details of USP47 regulation, substrate recognition, and the hotspots for drug discovery by targeting USP47.

PubMed: 37740002
DOI: 10.1038/s42003-023-05345-5

Experimental method

X-RAY DIFFRACTION (3 Å)