title: IDENTIFICATION OF CONOIDIN A AS A COVALENT INHIBITOR OF PEROXIREDOXIN II.
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.
authors.affiliation: Department of Microbiology and Molecular Genetics, 316 Stafford Hall, University of Vermont, 95 Carrigan Drive, Burlington VT 05405, USA.
authors.forename: Jeralyn D
authors.initials: JD
authors.lastname: Haraldsen
authors.forename: Gu
authors.initials: G
authors.lastname: Liu
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Botting
authors.forename: Jeffrey G A
authors.initials: JG
authors.lastname: Walton
authors.forename: Janet
authors.initials: J
authors.lastname: Storm
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Phalen
authors.forename: Lai Yu
authors.initials: LY
authors.lastname: Kwok
authors.forename: Dominique
authors.initials: D
authors.lastname: Soldati-Favre
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Heintz
authors.forename: Sylke
authors.initials: S
authors.lastname: Müller
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Westwood
authors.forename: Gary E
authors.initials: GE
authors.lastname: Ward