title: Plasmodium falciparum histidine-rich protein-2 (PfHRP2) modulates the redox activity of ferri-protoporphyrin IX (FePPIX): peroxidase-like activity of the PfHRP2-FePPIX complex.
abstract: Histidine-rich protein-2 from Plasmodium falciparum (PfHRP2) binds up to 50 molecules of ferri-protoporphyrin IX (FePPIX) (Choi, C. Y., Cerda, J. F., Chu, H. A., Babcock, G. T., and Marletta, M. A. (1999) Biochemistry 38, 16916-16924). We reasoned that the PfHRP2-FePPIX complex has antioxidant properties that could be beneficial to the parasite. Therefore, we examined whether binding to PfHRP2 modulated the redox properties of FePPIX. We observed that PfHRP2 completely inhibited the auto-oxidation of ascorbate mediated by free FePPIX. We also investigated the peroxidase activity of PfHRP2-FePPIX using 13-hydroperoxy-9,11-octadienoate (18:2-OOH) as substrate. Reaction of PfHRP2-FePPIX with 18:2-OOH in the presence of added reducing agents gave 13-hydroxy-9,11-octadienoate (18:2-OH) as a major product and 13-keto-9,11-octadienoate (18:2=O) and 9,12,13-trihydroxy-10-octadecaenoate as minor products. Binding of FePPIX to PfHRP2 lowered the rate of decomposition of 18:2-OOH and increased the 18:2-OH to 18:2=O ratio. Similar to other authentic peroxidases, phenols, amines, and biological reductants like ascorbate promoted 18:2-OH production, and NaCN inhibited 18:2-OH production. Thioanisole also acted as a reductant and was converted to thioanisole sulfoxide, suggesting formation of compound I during the reaction. These data show that PfHRP2 modulates the redox activity of FePPIX and that the PfHRP2-FePPIX complex may have previously unrecognized antioxidant properties.
authors.affiliation: Biochemistry Group, The Heart Research Institute, 145 Missenden Road, Camperdown, New South Wales 2050, Australia.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Mashima
authors.forename: Leann
authors.initials: L
authors.lastname: Tilley
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Siomos
authors.forename: Vicki
authors.initials: V
authors.lastname: Papalexis
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Raftery
authors.forename: Roland
authors.initials: R
authors.lastname: Stocker
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006427:Hemin / Q000378:metabolism*; D007700:Kinetics; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D000099053:Histidine-Rich Glycoprotein
chemical_list: D011506:Proteins; D011994:Recombinant Proteins; D000099053:Histidine-Rich Glycoprotein; D006427:Hemin; D010544:Peroxidases