Interaction of iron(II)-heme and artemisinin with a peptide mimic of Plasmodium falciparum HRP-II.
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.
Accardo
Antonella
A
Laboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, 31077 Toulouse Cedex 4, France.
Laurent
Sophie A-L
SA
Mazarguil
Honoré
H
Meyer
Michel
M
Robert
Anne
A
Meunier
Bernard
B
D000818:Animals; D037621:Artemisinins / Q000737:chemistry* / Q000378:metabolism; D006418:Heme / Q000737:chemistry* / Q000378:metabolism; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008956:Models, Chemical; D018716:Molecular Mimicry; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D000099053:Histidine-Rich Glycoprotein
D037621:Artemisinins; D010455:Peptides; D011506:Proteins; D015800:Protozoan Proteins; D000099053:Histidine-Rich Glycoprotein; D006418:Heme; C031327:artemisinin; D007501:Iron