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Molecular cloning and sequence analysis of the Plasmodium falciparum dihydrofolate reductase-thymidylate synthase gene.
Open accessAbstract
Genomic DNA clones that coded for the bifunctional dihydrofolate reductase (DHFR) and thymidylate synthase (TS) (DHFR-TS) activities from a pyrimethamine-sensitive strain of Plasmodium falciparum were isolated and sequenced. The deduced DHFR-TS protein contained 608 amino acids (71,682 Da). The coding region for DHFR-TS contained no intervening sequences and had a high A + T content (75%). The DHFR domain, in the amino-terminal portion of the protein, was joined by a 94-amino acid junction sequence to the TS domain in the carboxyl-terminal portion of the protein. The TS domain was more conserved than the DHFR domain and both P. falciparum domains were more homologous to eukaryotic than to prokaryotic forms of the enzymes. Predicted secondary structures of the DHFR and TS domains were nearly identical to the structures identified in other DHFR and TS enzymes.
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Cited by
Mechanisms 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
Peterson, D. S., Milhous, W. K., & Wellems, T. E. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.8.3018 · Cited by 419
Nzila, A. M., Mberu, E. K., Sulo, J., Dayo, H., Winstanley, P. A., Sibley, C. H., & Watkins, W. M. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.4.991-996.2000 · Cited by 232
Urban, P., & Fernandez-Busquets, X. (2014) · Current Medicinal Chemistry · doi:10.2174/09298673113206660292 · Cited by 39
Metadata
- Authors
- Bzik, D. J., Li, W. B., Horii, T., & Inselburg, J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1987-12
- Volume
- 84
- Issue
- 23
- Pages
- 8360-8364
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2050341196
- Cited by
- 258
- References
- 0
- FWCI
- 20.04
- Type
- journal article
- Language
- en
- Open access
- green
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- Bzik, D. J., Li, W. B., Horii, T., & Inselburg, J. (1987). Molecular cloning and sequence analysis of the Plasmodium falciparum dihydrofolate reductase-thymidylate synthase gene. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.84.23.8360
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