Chen, P

Deng, ZS

Ding, Y

GAO, P

Heck, AJR

Kao, RYT

Lee, OY

Rose, RJ

Tao, X

Yang, D

ZHANG, ZF

Zhao, H

ZHAO, Q

The natural products triptolide, withaferin A and celastrol have been discovered to be novel Prx I chaperone inhibitors using synthetic chemical probes.</p

Qian Zhao

Yu Ding

Zhangshuang Deng

On-Yi Lee

Peng Gao

Pin Chen

Rebecca J. Rose

Hong Zhao

Zhehao Zhang

Xin-Pei Tao

Albert J. R. Heck

Richard Kao

Dan Yang

Crossref

Chemical Science

Natural products triptolide, celastrol, and withaferin A inhibit the chaperone activity of peroxiredoxin I

HKU Scholars Hub

Peroxiredoxin I (Prx I) plays an important role in cancer development and inflammation. It is a dual-functional protein which acts as both an antioxidant enzyme and a molecular chaperone. While there have been intensive studies on its peroxidase activity, Prx I's chaperone activity remains elusive, likely due to the lack of chaperone inhibitors. Here we report that natural product triptolide selectively inhibits the chaperone activity of Prx I, but not its peroxidase activity. Through direct interaction with corresponding cysteines, triptolide triggers dissociation of high-molecular-weight oligomers of Prx I, and thereby inhibits its chaperone activity in a dose-dependent manner. We have also identified celastrol and withaferin A as novel Prx I chaperone inhibitors that are even more potent than triptolide in the chaperone activity assay. By revealing the exact molecular mechanisms of interaction and inhibition, the current study provides the first Prx I chaperone inhibitors as promising pharmacological tools for modulating and dissecting the chaperone function of Prx I

Zhao, Qian

Ding, Yu

Deng, Zhangshuang

Lee, On Yi

Gao, Peng

Chen, Pin

Rose, Rebecca J.

Zhao, Hong

Zhang, Zhehao

Tao, Xin Pei

Heck, Albert J R

Kao, Richard

Yang, Dan

Biomolecular Mass Spectrometry and Proteomics

Sub Biomol.Mass Spectrometry & Proteom.

Sub Biomol.Mass Spect. and Proteomics

NARCIS 

Natural products triptolide, celastrol, and withaferin A inhibit the chaperone activity of peroxiredoxin i

Utrecht University Repository

http://hub.hku.hk/bitstream/10722/220597/1/content.pdf

Natural products triptolide, celastrol, and withaferin A inhibit the chaperone activity of peroxiredoxin I

Abstract

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Crossref

HKU Scholars Hub

NARCIS

Utrecht University Repository