Glutathione S-Transferase of the Malarial Parasite Plasmodium falciparum: Characterization of a Potential Drug Target

2002 ◽  
Vol 383 (5) ◽  
Author(s):  
Petra Harwaldt ◽  
Stefan Rahlfs ◽  
Katja Becker
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Target ◽  
Malarial Parasite ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Glutathione S Transferase ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

The selenoproteome of the malarial parasite Plasmodium falciparum as potential drug target

2006 ◽  
Vol 2006 (Spring) ◽  
Author(s):  
Rimma Iozef ◽  
Beate Hecker ◽  
Stefan Rahlfs ◽  
Alexey V. Lobanov ◽  
Stephan Gromer ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Target ◽  
Malarial Parasite ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

scholarly journals X-ray structure of glutathione S-transferase from the malarial parasite Plasmodium falciparum

2003 ◽  
Vol 100 (24) ◽  
pp. 13821-13826 ◽  
Author(s):  
K. Fritz-Wolf ◽  
A. Becker ◽  
S. Rahlfs ◽  
P. Harwaldt ◽  
R. H. Schirmer ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malarial Parasite ◽  
Glutathione S Transferase ◽  
X Ray ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

scholarly journals Differential Stimulation of the Na+/H+ Exchanger Determines Chloroquine Uptake in Plasmodium falciparum

1998 ◽  
Vol 140 (2) ◽  
pp. 335-345 ◽  
Author(s):  
Stefan Wünsch ◽  
Cecilia P. Sanchez ◽  
Michael Gekle ◽  
Lars Große-Wortmann ◽  
Jochen Wiesner ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malarial Parasite ◽  
Physiological Data ◽  
Ph Measurements ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Transitory Phase ◽  
Identification And Characterization

Here we describe the identification and characterization of a physiological marker that is associated with the chloroquine-resistant (CQR) phenotype in the human malarial parasite Plasmodium falciparum. Single cell in vivo pH measurements revealed that CQR parasites consistently have an elevated cytoplasmic pH compared to that of chloroquine-sensitive (CQS) parasites because of a constitutively activated Na+/H+ exchanger (NHE). Together, biochemical and physiological data suggest that chloroquine activates the plasmodial NHE of CQS parasites, resulting in a transitory phase of rapid sodium/hydrogen ion exchange during which chloroquine is taken up by this protein. The constitutively stimulated NHE of CQR parasites are capable of little or no further activation by chloroquine. We propose that the inability of chloroquine to stimulate its own uptake through the constitutively activated NHE of resistant parasites constitutes a minimal and necessary event in the generation of the chloroquine-resistant phenotype.

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.

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