2004 Fiscal Year Final Research Report Summary
Mechanistic investigation for neutralization of toxic heme by histidine rich protein (HRP2) of malaria parasite using a series of HRP2 model peptides
| Project/Area Number |
15550146
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Chemistry related to living body
|
|---|
| Research Institution | Kyoto Institute of Technology |
|---|
Principal Investigator |
TAJIMA Kunihiko Kyoto Institute of Technology, Faculty of Textile, Professor, 繊維学部, 教授 (50163457)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | Malaria / heme / HRP2 / heme-HRP2 complex / ESR / coordination |
|---|
| Research Abstract |
A series of model peptides, 9 to 27-mer, of Plasmodium Falciparum histidine rich protein 2(HRP2). The coordination reactions occurring between these peptides and ferric iron complex of meso-porphyrin (Fe(III)MP) were studied by using optical absorption measurements and electron spin resonance spectroscopy at 4.2 K. Based on the optical spectrometric titration, the dissociation constants for the heme-peptide complexes were evaluated. The longest peptide 27-R (three repeat of reciprocal sequence of HRP2 ; Ala-His-His-Ala-His-His-Ala-Ala-Asp), Ala-His-His-Ala-His-His-Ala-Ala-Asp-His-His-Ala-His-His-Ala-His-His-Ala-Ala-Asp-Ala-His-His-Ala-His-His-Ala-Ala-Asp, showed significantly high Kd value as 0.97 μM, which correspond to that of naturally occurring HRP2 (0.77 μM). The Kd values of the peptides revealed concomitant decrease with decrease of the number of His residue, for example, the Kd value of the shortest prptide 10R (Ala-His-His-Ala-Ala-Asp-Ala-His-His-Ala) was evaluated to be 77 mM. The both 27R- and 10R-Fe(III)MP complexes gave an identical absorption maxima (405, 533, and 564 nm) ascribed to be the six coordinate iron porphyrin complex. Taking into account the results of ESR spectroscopy, the both axial ligands of these complexes were identified to be nitrogen atoms of imidazole moiety of His.
|
