8ITP

Crystal structure of USP47 catalytic domain complex with ubiquitin

8ITP の概要

• エントリーDOI: 10.2210/pdb8itp/pdb
• 分子名称: Ubiquitin, Ubiquitin carboxyl-terminal hydrolase 47, ZINC ION (3 entities in total)
• 機能のキーワード: ubiquitin specific protease, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 132420.25

構造登録者

Kim, E.E.,Shin, S.C. (登録日: 2023-03-22, 公開日: 2024-03-27, 最終更新日: 2024-05-08)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3 Å)