Metabolic enzymes as potential drug targets in Plasmodium falciparum.
Plasmodium falciparum causes the most severe form of malaria that is fatal in many cases. Emergence of drug resistant strains of P. falciparum requires that new drug targets be identified. This review considers in detail enzymes of the glycolytic pathway, purine salvage pathway, pyrimidine biosynthesis and proteases involved in catabolism of haemoglobin. Structural features of P. falciparum triosephosphate isomerase which could be exploited for parasite specific drug development have been highlighted. Utility of P. falciparum hypoxanthine-guanine-phosphoribosyltransferase, adenylosuccinate synthase, dihydroorotate dehydrogenase, thymidylate synthase-dihydrofolate reductase, cysteine and aspartic proteases have been elaborated in detail. The review also briefly touches upon other potential targets in P. falciparum.
Subbayya
I N
IN
Molecular Biophysics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore.
Ray
S S
SS
Balaram
P
P
Balaram
H
H
D000818:Animals; D004798:Enzymes / Q000378:metabolism*; D006019:Glycolysis; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism
D004798:Enzymes; D006454:Hemoglobins; D015800:Protozoan Proteins; D011743:Pyrimidines