Identification of conoidin A as a covalent inhibitor of peroxiredoxin II

Jeralyn D. Haraldsen; Gu Liu; Catherine H. Botting; Jeffrey G. A. Walton; Janet Storm; Timothy J. Phalen; Lai Yu Kwok; Dominique Soldati-Favre; Nicholas H. Heintz; Sylke Müller; Nicholas J. Westwood; Gary E. Ward

doi:10.1039/B901735F

skip RSC | ChemSpider | Feedback

Home > Journals > Organic & Biomolecular ... > Identification of conoi...

Authors & Referees | Librarians

You do not have JavaScript enabled. Please enable JavaScript to access the full features of the site or access our non-JavaScript page.

Organic & Biomolecular Chemistry

Issue 15, 2009

More about this Journal
Editorial Board
Submit an Article

Follow Journal | |

Journal Home | RSC Journals

Paper

Previous Article | Next Article

Identification of conoidin A as a covalent inhibitor of peroxiredoxin II

Jeralyn D. Haraldsen , Gu Liu , Catherine H. Botting , Jeffrey G. A. Walton , Janet Storm , Timothy J. Phalen , Lai Yu Kwok , Dominique Soldati-Favre , Nicholas H. Heintz , Sylke Müller , Nicholas J. Westwood and Gary E. Ward

Org. Biomol. Chem., 2009, 7, 3040-3048

DOI: 10.1039/B901735F
Received 27 Jan 2009, Accepted 31 Mar 2009
First published on the web 21 May 2009

Please wait while Download options loads

Request Permissions

Abstract
Cited by
Compounds
Related Content

Conoidin A (1) is an inhibitor of host cell invasion by the protozoan parasite Toxoplasma gondii. In the course of studies aimed at identifying potential targets of this compound, we determined that it binds to the T. gondii enzyme peroxiredoxin II (TgPrxII). Peroxiredoxins are a widely conserved family of enzymes that function in antioxidant defense and signal transduction, and changes in PrxII expression are associated with a variety of human diseases, including cancer. Disruption of the TgPrxII gene by homologous recombination had no effect on the sensitivity of the parasites to 1, suggesting that TgPrxII is not the invasion-relevant target of 1. However, we showed that 1 binds covalently to the peroxidatic cysteine of TgPrxII, inhibiting its enzymatic activity in vitro. Studies with human epithelial cells showed that 1 also inhibits hyperoxidation of human PrxII. These data identify Conoidin A as a novel inhibitor of this important class of antioxidant and redox signaling enzymes.

This may take some time to load.

Terms & Conditions|Privacy |Accessibility|ACAP Enabled

Organic & Biomolecular Chemistry

Identification of conoidin A as a covalent inhibitor of peroxiredoxin II

Log in (Free Access)

Log in (Subscriber Access)

Supplementary Info

Articles By