Studies on Plasmepsins I and II from the Malarial Parasite Plasmodium falciparum and their Exploitation as Drug Targets

1998 ◽  
pp. 397-406 ◽  
Author(s):  
Richard P. Moon ◽  
Daniel Bur ◽  
Hansruedi Loetscher ◽  
Allan D’Arcy ◽  
Lorraine Tyas ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Targets ◽  
Malarial Parasite ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

scholarly journals Localization of ferrochelatase in Plasmodium falciparum

2004 ◽  
Vol 384 (2) ◽  
pp. 429-436 ◽  
Author(s):  
Sundaramurthy VARADHARAJAN ◽  
B. K. Chandrashekar SAGAR ◽  
Pundi N. RANGARAJAN ◽  
Govindarajan PADMANABAN
Keyword(s):  
Plasmodium Falciparum ◽  
De Novo ◽  
Enzymic Activity ◽  
Malarial Parasite ◽  
Parasite Genome ◽  
Marker Proteins ◽  
Parasite Plasmodium ◽  
Theoretical Predictions ◽  
Parasite Plasmodium Falciparum

Our previous studies have demonstrated de novo haem biosynthesis in the malarial parasite (Plasmodium falciparum and P. berghei). It has also been shown that the first enzyme of the pathway is the parasite genome-coded ALA (δ-aminolaevulinate) synthase localized in the parasite mitochondrion, whereas the second enzyme, ALAD (ALA dehydratase), is accounted for by two species: one species imported from the host red blood cell into the parasite cytosol and another parasite genome-coded species in the apicoplast. In the present study, specific antibodies have been raised to PfFC (parasite genome-coded ferrochelatase), the terminal enzyme of the haem-biosynthetic pathway, using recombinant truncated protein. With the use of these antibodies as well as those against the hFC (host red cell ferrochelatase) and other marker proteins, immunofluorescence studies were performed. The results reveal that P. falciparum in culture manifests a broad distribution of hFC and a localized distribution of PfFC in the parasite. However, PfFC is not localized to the parasite mitochondrion. Immunoelectron-microscopy studies reveal that PfFC is indeed localized to the apicoplast, whereas hFC is distributed in the parasite cytoplasm. These results on the localization of PfFC are unexpected and are at variance with theoretical predictions based on leader sequence analysis. Biochemical studies using the parasite cytosolic and organellar fractions reveal that the cytosol containing hFC accounts for 80% of FC enzymic activity, whereas the organellar fraction containing PfFC accounts for the remaining 20%. Interestingly, both the isolated cytosolic and organellar fractions are capable of independent haem synthesis in vitro from [4-14C]ALA, with the cytosol being three times more efficient compared with the organellar fraction. With [2-14C]glycine, most of the haem is synthesized in the organellar fraction. Thus haem is synthesized in two independent compartments: in the cytosol, using the imported host enzymes, and in the organellar fractions, using the parasite genome-coded enzymes.

scholarly journals Molecular cloning, characterization and localization of PfPK4, an eIF-2α kinase-related enzyme from the malarial parasite Plasmodium falciparum

1997 ◽  
Vol 328 (2) ◽  
pp. 677-687 ◽  
Author(s):  
Jörg J. MÖHRLE ◽  
Yi ZHAO ◽  
Barbara WERNLI ◽  
M. Richard FRANKLIN ◽  
Barbara KAPPES
Keyword(s):  
Amino Acids ◽  
Plasmodium Falciparum ◽  
Protein Kinase ◽  
Protein Kinases ◽  
Initiation Factor ◽  
Malarial Parasite ◽  
Kinase Gene ◽  
Western Blots ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

PfPK4, a protein kinase gene from the human malarial parasite Plasmodium falciparum, has been cloned utilizing oligonucleotide probing. The gene encodes a protein of a predicted length of 1123 amino acids, and within this amino acid sequence all the conserved regions characteristic of protein kinases can be identified. The catalytic kinase domain possesses highest identities (34-37%) with eukaryotic initiation factor-2α (eIF-2α) kinases, especially haem-regulated inhibitory (HRI) protein kinases. There are two kinase inserts in PfPK4, located at positions common to eIF-2α kinases. The first insert separates kinase subdomains IV and VI by 559 amino acids, and the second subdomains VII and VIII by 41 amino acids. Both inserts are larger than their homologues in eIF-2α kinases. The sequence of PfPK4 has one putative haemin-binding site. The recombinant protein, expressed in Escherichia coli, phosphorylates a synthetic peptide representing a substrate of eIF-2α kinases. Autophosphorylation and substrate phosphorylation are inhibited by haemin. Thus PfPK4 appears to be the first protozoan protein kinase related to eIF-2α kinases and might be the first non-mammalian HRI kinase. Western blots indicated that the protein is expressed as major forms of 80 and 90 kDa. Whereas the 80 kDa form is present throughout the intraerythrocytic development and in merozoites, the two 90 kDa forms are only found in mature parasites. One of the latter is also present in the membrane fraction of erythrocytes harbouring segmenters. Confocal microscopy detected the protein distributed throughout the trophozoite, whereas it was found in discrete foci (punctate distribution) in segmenters. PfPK4 co-localizes with P. falciparum 83 kDa antigen/apical membrane antigen-1 at the apical complex in segmenters and merozoites, but does not co-localize with rhoptry-associated protein-1.

scholarly journals Reduced deformability of thalassemic erythrocytes and erythrocytes with abnormal hemoglobins and relation with susceptibility to Plasmodium falciparum invasion

Blood ◽  
1992 ◽  
Vol 79 (9) ◽  
pp. 2460-2463 ◽  
Author(s):  
A Bunyaratvej ◽  
P Butthep ◽  
N Sae-Ung ◽  
S Fucharoen ◽  
Y Yuthavong
Keyword(s):  
Plasmodium Falciparum ◽  
Clinical Symptoms ◽  
Malarial Parasite ◽  
Beta Thalassemia ◽  
Cell Deformability ◽  
Intact Cells ◽  
Laser Diffractometry ◽  
Parasite Plasmodium ◽  
Hb E ◽  
Parasite Plasmodium Falciparum

Abstract A number of genetically variant erythrocytes showed decreased deformability of both intact cells and membranes prepared therefrom as measured by laser diffractometry. Erythrocytes associated with minor or no clinical symptoms (eg, alpha-thalassemia traits, hemoglobin [Hb] E trait, Hb Constant Spring trait), which showed only a minimal decrease in deformability, were, in general, invaded efficiently by the malarial parasite Plasmodium falciparum. Other variant erythrocytes (beta- thalassemia/Hb E, homozygous Hb E, homozygous Hb Constant Spring, Hb H, Hb H/Hb Constant Spring) with low deformability showed different degrees of reduction in invasion susceptibility, most of which were less than proportional with deformability decrease. It is concluded that parasite invasion is only weakly related to gross cell deformability, which in turn depends on various factors other than membrane deformability.

The mechanism of erythrocyte invasion by the malarial parasite, Plasmodium falciparum

2011 ◽  
Vol 22 (9) ◽  
pp. 953-960 ◽  
Author(s):  
Rachel E. Farrow ◽  
Judith Green ◽  
Zoe Katsimitsoulia ◽  
William R. Taylor ◽  
Anthony A. Holder ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malarial Parasite ◽  
Erythrocyte Invasion ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum
Sign in / Sign up

Export Citation Format

Share Document