6533b7d6fe1ef96bd1265d48

RESEARCH PRODUCT

Interaction of iron(II)-heme and artemisinin with a peptide mimic of Plasmodium falciparum HRP-II

Antonella AccardoHonoré MazarguilSophie LaurentMichel MeyerBernard MeunierAnne Robert

subject

Heme bindingStereochemistryIronPlasmodium falciparumProtozoan ProteinsmalariaPeptide010402 general chemistry01 natural sciencesBiochemistryInorganic Chemistry03 medical and health scienceschemistry.chemical_compoundResidue (chemistry)[ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM]hemozoinAnimals[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM]hemeHemealkylationHistidineComputingMilieux_MISCELLANEOUS030304 developmental biologychemistry.chemical_classification0303 health sciencesMolecular StructurebiologyHemozoinMolecular MimicryProteinsPlasmodium falciparumbiology.organism_classificationArtemisininsProtein tertiary structure3. Good health0104 chemical sciencesKineticsModels ChemicalchemistryBiochemistryartemisininPeptidesProtein Binding

description

Abstract The interaction of heme or heme-artemisinin adducts (heme-art) with different peptides mimicking repeat sequences of the Histidine-Rich-Protein-II of Plasmodium falciparum (PfHRP-II) was investigated. The pseudo-first order rate constants of the coordination of heme or heme-art onto a histidine rich peptide, used as a mimic of PfHRP-II putative heme binding sequence, are of the same order of magnitude, namely 42 and 14 s −1 , respectively. Despite the intrinsic reactivity of the carbonyl at C10 of heme-art toward a hydroxyl function, a peptide containing a serine or threonine residue does not readily react with heme-art adducts. Therefore, a much higher affinity of heme-art compared to heme toward PfHRP-II, if so, must be induced by a specific interaction or a chemical reaction, these phenomena being both due to the tertiary structure of the parasite protein itself.

https://hal.archives-ouvertes.fr/hal-00460812