P. falciparum pro-histoaspartic protease (proHAP) protein peptides bind specifically to erythrocytes and inhibit the invasion process in vitro
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John Valbuena
, Ricardo Vera , Alvaro Puentes , Marisol Ocampo , Javier Garcia , Hernando Curtidor , Ramses Lopez , Luis Rodriguez , Jaiver Rosas , Jimena Cortes , Martha Forero , Martha Pinto und Manuel Elkin Patarroyo
Abstract
Plasmodium falciparum histoaspartic protease (HAP) is an active enzyme involved in haemoglobin degradation. HAP is expressed as an inactive 51-kDa zymogen and is cleaved into an active 37-kDa enzyme. It has been proposed that this kind of protease might be implicated in the parasite's invasion of erythrocytes; however, this protein's role during invasion has still to be determined. Synthetic peptides derived from the HAP precursor (proHAP) were tested in erythrocyte binding assays to identify their possible function in the invasion process. Two proHAP high-activity binding peptides (HABPs) specifically bound to erythrocytes; these peptides were numbered 30609 (101LKNYIKESVKLFNKGLTKKS120) and 30610 (121YLGSEFDNVELKDLANVLSF140). The binding of these two peptides was saturable, presenting nanomolar affinity constants. These peptides interacted with 26- and 45-kDa proteins on the erythrocyte surface; the nature of these receptor sites was studied in peptide binding assays using enzyme-treated erythrocytes. The HABPs showed greater than 90% merozoite invasion inhibition in in vitro assays. Goat serum containing proHAP polymeric peptide antibodies inhibited parasite invasion in vitro.
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- Supplementary material to the paper “The connexin gene family in mammals”
- Nicking activity on pBR322 DNA of ribosome inactivating proteins from Phytolacca dioica L. leaves
- Identification of three novel mutations in the dihydropyrimidine dehydrogenase gene associated with altered pre-mRNA splicing or protein function
- The connexin gene family in mammals
- Hydrogen peroxide causes greater oxidation in cellular RNA than in DNA
- Homology modeling and SAR analysis of Schistosoma japonicum cathepsin D (SjCD) with statin inhibitors identify a unique active site steric barrier with potential for the design of specific inhibitors
- Interpretation of the reactivity of peroxidase compound II with phenols and anilines using the Marcus equation
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