Structural and Functional Characterization of USP47 Reveals a Hot Spot for Inhibitor Design

Overview

Journal Commun Biol

Specialty Biology

Date 2023 Sep 22

PMID 37740002

Authors

Sang Chul Shin

Jinyoung Park

Kyung Hee Kim

Jung Min Yoon

Jinhong Cho

Byung Hak Ha

Yeonji Oh

Hyunah Choo

Eun Joo Song

Eunice EunKyeong Kim

Affiliations

Soon will be listed here.

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.

Citing Articles

Deubiquitinases as novel therapeutic targets for diseases.

Xian Y, Ye J, Tang Y, Zhang N, Peng C, Huang W MedComm (2020). 2024; 5(12):e70036.

PMID: 39678489 PMC: 11645450. DOI: 10.1002/mco2.70036.

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