Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum.

作者: A. F. Cowman , M. J. Morry , B. A. Biggs , G. A. Cross , S. J. Foote

DOI: 10.1073/PNAS.85.23.9109

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摘要: Abstract We describe the isolation and sequence of gene for bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS; EC 1.5.1.3 2.1.1.45, respectively) from two pyrimethamine-resistant clones Plasmodium falciparum, HB3 7G8. We have also derived DHFR portion gene, by amplification using polymerase chain reaction, pyrimethamine-sensitive clone 3D7 strains V-1, K-1, Csl-2, Palo-alto. The deduced protein resistant contained a single amino acid difference 3D7. It is highly likely that this involved in mechanism drug resistance HB3. other contains same sensitive However, they all differ at one site may influence pyrimethamine resistance. DHFR-TS present as copy on chromosome 4 isolates tested. Therefore, molecular basis parasites tested not gene.

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