Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human malaria parasites (Plasmodium falciparum) grown in continuous erythrocyte culture utilize hypoxanthine for synthesis of both guanosine and adenosine nucleotides. Unlike the mature human erythrocyte, the malaria parasite depends on a constant supply of guanylates, primarily for synthesis of nucleic acids. This parasite specific requirement for guanylates led us to predict that a block in the hypoxanthine to guanosine monophosphate pathway would be selectively lethal to the parasite. Bredinin (4-carbamoyl-1-beta-D-ribofuranyosyl-imidazolium-5-olate) inhibited the synthesis of guanosine monophosphate from inosine monophosphate by parasitized erythrocytes. This block in guanylate synthesis was fatal to both a drug-sensitive (FCR-3) and a drug-resistant (VNS) strain of the malaria parasite at a bredinin concentration of 50 microM, arresting growth of the parasite at the trophozoite stage of development. These studies emphasize the essential role of guanylates and their synthesis from hypoxanthine in the metabolism of malaria parasite. They further suggest that bredinin or similar agents that selectively interfere with parasite guanylate metabolism may have potential for antimalarial chemotherapy.
 ...
PMID:Antimalarial properties of bredinin. Prediction based on identification of differences in human host-parasite purine metabolism. 704 69

After invasion of red blood cells, malaria matures within the cell by degrading hemoglobin avidly. For enormous protein breakdown in trophozoite stage, many efficient and ordered proteolysis networks have been postulated and exploited. In this study, a potential interaction of a 60-kDa Plasmodium falciparum (Pf)-heat shock protein (Hsp60) and Pf-calpain, a cysteine protease, was explored. Pf-infected RBC was isolated and the endogenous Pf-Hsp60 and Pf-calpain were determined by western blot analysis and similar antigenicity of GroEL and Pf-Hsp60 was determined with anti-Pf-Hsp60. Potential interaction of Pf-calpain and Pf-Hsp60 was determined by immunoprecipitation and immunofluorescence assay. Mizoribine, a well-known inhibitor of Hsp60, attenuated both Pf-calpain enzyme activity as well as P. falciparum growth. The presented data suggest that the Pf-Hsp60 may function on Pf-calpain in a part of networks during malaria growth.
...
PMID:Potential Interaction of Plasmodium falciparum Hsp60 and Calpain. 2679 32