The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria.
Open accessAbstract
Analysis of a genetic cross of Plasmodium falciparum and of independent parasite isolates from Southeast Asia, Africa, and South America indicates that resistance to pyrimethamine, an antifolate used in the treatment of malaria, results from point mutations in the gene encoding dihydrofolate reductase-thymidylate synthase (EC 1.5.1.3 and EC 2.1.1.45, respectively). Parasites having a mutation from Thr-108/Ser-108 to Asn-108 in DHFR-TS are resistant to the drug. The Asn-108 mutation occurs in a region analogous to the C alpha-helix bordering the active site cavity of bacterial, avian, and mammalian enzymes. Additional point mutations (Asn-51 to Ile-51 and Cys-59 to Arg-59) are associated with increased pyrimethamine resistance and also occur at sites expected to border the active site cavity. Analogies with known inhibitor/enzyme structures from other organisms suggest that the point mutations occur where pyrimethamine contacts the enzyme and may act by inhibiting binding of the drug.
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Citations
Cites
Primer-Directed Enzymatic Amplification of DNA with a Thermostable DNA Polymerase
Saiki, R. K., Gelfand, D. H., Stoffel, S., Scharf, S. J., Higuchi, R., Horn, G. T., Mullis, K. B., & Erlich, H. A. (1988) · Science · doi:10.1126/science.2448875 · Cited by 17,719
Cited by
Su, X.-Z., Heatwole, V. M., Wertheimer, S. P., Guinet, F., Herrfeldt, J. A., Peterson, D. S., Ravetch, J. A., & Wellems, T. E. (1995) · Cell · doi:10.1016/0092-8674(95)90055-1 · Cited by 1,219
Self-citationMechanisms of Resistance of Malaria Parasites to Antifolates
Gregson, A., & Plowe, C. V. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.1.4 · Cited by 499
Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia
Miotto, O., Almagro-Garcia, J., Manske, M., MacInnis, B., Campino, S., Rockett, K. A., Amaratunga, C., Lim, P., Suon, S., Sreng, S., et al. (2013) · Nature Genetics · doi:10.1038/ng.2624 · Cited by 462
Plasmodium—a brief introduction to the parasites causing human malaria and their basic biology
Sato, S. (2021) · Journal of Physiological Anthropology · doi:10.1186/s40101-020-00251-9 · Cited by 404
Brooks, D. R., Wang, P., Read, M., Watkins, W. M., Sims, P. F. G., & Hyde, J. E. (1994) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1994.00397.x · Cited by 369
Metadata
- Authors
- Peterson, D. S., Walliker, D., & Wellems, T. E.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1988-12
- Volume
- 85
- Issue
- 23
- Pages
- 9114-9118
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2081729133
- Cited by
- 653
- References
- 1
- FWCI
- 15.32
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. https://app.cochat.ai/papers/10.1073/pnas.85.23.9114
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- Peterson, D. S., Walliker, D., & Wellems, T. E. (1988). Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.85.23.9114
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