Study of dihydrofolate reductase-thymidylate synthase in Plasmodium falciparum |
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Authors: | J Inselburg R D Zhang |
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Affiliation: | Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire 03756. |
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Abstract: | 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. |
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