Integrated Mass Spectrometry Reveals Celastrol As a Novel Catechol-O-methyltransferase Inhibitor

Haijun Guo, Yang Yang, Qi Zhang, Jie-Ren Deng, Ying Yang, Shuqi Li, Pui-Kin So, Thomas C. Lam, Man-kin Wong, Qian Zhao (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

6 Citations (Scopus)

Abstract

Natural product celastrol is known to have various biological activities, yet its molecular targets that correspond to many activities remain unclear. Here, we used multiple mass-spectrometry-based approaches to identify catechol-O-methyltransferase (COMT) as a major binding target of celastrol and characterized their interaction comprehensively. Celastrol was found to inhibit the enzymatic activity of COMT and increased the dopamine level in neuroendocrine chromaffin cells significantly. Our study not only revealed a novel binding target of celastrol but also provided a new scaffold and cysteine hot spot for developing new generation COMT inhibitors in combating neurological disorders.
Original languageEnglish
Pages (from-to)2003-2009
Number of pages7
JournalACS Chemical Biology
Volume17
Issue number8
DOIs
Publication statusPublished - 18 Mar 2022

Fingerprint

Dive into the research topics of 'Integrated Mass Spectrometry Reveals Celastrol As a Novel Catechol-O-methyltransferase Inhibitor'. Together they form a unique fingerprint.

Cite this