Structure, Function, and Inhibitors of the Mitochondrial Chaperone TRAP1

Soosung Kang, Byoung Heon Kang

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations

Abstract

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial molecular chaperone modulating cellular metabolism and signaling pathways by altering the conformation, activity, and stability of numerous substrate proteins called clients. It exerts its chaperone function as an adaptive response to counter cellular stresses instead of maintaining housekeeping protein homeostasis. However, the stress-adaptive machinery becomes dysregulated to support the progression and maintenance of human diseases, such as cancers; therefore, TRAP1 has been proposed as a promising target protein for anticancer drug development. In this review, by collating recent reports on high-resolution TRAP1 structures and structure-activity relationships of inhibitors, we aimed to provide better insights into the chaperoning mechanism of the emerging drug target and to suggest an efficient strategy for the development of potent TRAP1 inhibitors.

Original languageEnglish
Pages (from-to)16155-16172
Number of pages18
JournalJournal of Medicinal Chemistry
Volume65
Issue number24
DOIs
StatePublished - 22 Dec 2022

Bibliographical note

Funding Information:
S.K. is thankful for the National Research Foundation (NRF) of Korea grant funded by MSIT (NRF-2018R1A5A2025286, 2022M3E5F3080873, and 2019R1A2C2004142). B.H.K. is supported by the NRF funded by MSIT (2019R1A2C2086618, 2018R1A5A1024340, and 2022M3E5F2017408).

Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.

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