Identification of conoidin A as a covalent inhibitor of peroxiredoxin II

Haraldsen, J.D. et al. (2009) Identification of conoidin A as a covalent inhibitor of peroxiredoxin II. Organic and Biomolecular Chemistry, 7(15), pp. 3040-3048. (doi: 10.1039/b901735f)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Muller, Professor Sylke and Storm, Dr Janet
• Authors: Haraldsen, J.D., Liu, G., Botting, C.H., Walton, J.G.A., Storm, J., Phalen, T.J., Kwok, L.Y., Soldati-Favre, D., Heintz, N.H., Muller, S., Westwood, N.J., and Ward, G.E.
• Subjects: Q Science > QH Natural history > QH345 Biochemistry
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Organic and Biomolecular Chemistry
• ISSN: 1477-0520
• ISSN (Online): 1477-0539