Study of dihydrofolate reductase-thymidylate synthase in Plasmodium falciparum.
The production of the dihydrofolate reductase-thymidylate synthase (DHFR-TS) bifunctional protein of Plasmodium falciparum was measured in the wild type, pyrimethamine sensitive strain, FCR3, and in a pyrimethamine resistant mutant, FCR3-D7, which contains a DHFR-TS gene duplication that overproduces a mutant enzyme. The DHFR-TS content in both strains began to increase significantly from the early trophozoite stage through schizogony. The DHFR-TS content in either the ring or trophozoite-schizont stage parasites remained constant for at least 9 hr in the presence of protein synthesis-inhibitory levels of cycloheximide, which suggested that the measure of enzyme accumulation was a measure of enzyme synthesis. Actinomycin D treated parasites did not accumulate DHFR-TS which suggested that the DHFR-TS mRNA had a short half-life. DHFR-TS accumulated in the presence of aphidicolin inhibition of DNA synthesis which indicated that both syntheses could be uncoupled.
D000818:Animals; D016590:Aphidicolin; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D003609:Dactinomycin / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D013762:Tetrahydrofolate Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D013940:Thymidylate Synthase / Q000096:biosynthesis* / Q000235:genetics
D004224:Diterpenes; D003609:Dactinomycin; D016590:Aphidicolin; D004247:DNA; D003513:Cycloheximide; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase; D004257:DNA Polymerase II