Toxoplasma gondii: Generation of novel truncation mutations in the linker domain of dihydrofolate reductase-thymidylate synthase

Experimental Parasitology

Volumn 106, Issue 3-4, 2004, Pages 179-182

  Belperron, Alexia A ^a,d   Fox, Barbara A ^a   O'Neil, Robert H ^b   Peaslee, Kimberly A W ^b   Horii, Toshihiro ^c   Anderson, Amy C ^b   Bzik, David J ^a  

^a DARTMOUTH MEDICAL SCHOOL   (United States)

^b Dartmouth College   (United States)

^c OSAKA UNIVERSITY   (Japan)

^d YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; DIHYDROFOLATE REDUCTASE; METHOTREXATE; MUTANT PROTEIN; PLASMID VECTOR; PYRIMETHAMINE; THYMIDYLATE SYNTHASE;

AMINO ACID SEQUENCE; AMINO TERMINAL SEQUENCE; ARTICLE; CATALYSIS; CONTROLLED STUDY; DRUG PROTEIN BINDING; DRUG RESISTANCE; GENE CONSTRUCT; GENE MUTATION; GENETIC TRANSFECTION; GROWTH RATE; IC 50; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTOZOAL GENETICS; SITE DIRECTED MUTAGENESIS; TOXOPLASMA GONDII; TRANSGENICS;

AMINO ACID SEQUENCE; ANIMALS; ANTIPROTOZOAL AGENTS; BLOTTING, WESTERN; DRUG RESISTANCE; HUMANS; MODELS, GENETIC; MOLECULAR SEQUENCE DATA; MULTIENZYME COMPLEXES; MUTAGENESIS, INSERTIONAL; MUTATION; POINT MUTATION; POLYMERASE CHAIN REACTION; PYRIMETHAMINE; RESTRICTION MAPPING; SEQUENCE ALIGNMENT; TETRAHYDROFOLATE DEHYDROGENASE; THYMIDYLATE SYNTHASE; TOXOPLASMA; TRANSFECTION;

TOXOPLASMA GONDII;

EID: 2542439696     PISSN: 00144894     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.exppara.2004.03.002     Document Type: Article

References (21)

1. Belperron A.A., Fox B.A., Horii T., Bzik D.J. Toxoplasma gondii: genetic selection of tethered dihydrofolate reductase-thymidylate synthase fusion proteins. Experimental Parasitology. 98:2001;167-170
2. Bzik D.J., Li W.-B., Horii T., Inselburg J. Molecular cloning and sequence analysis of the Plasmodium falciparum dihydrofolate reductase-thymidylate synthase gene. Proceedings of the National Academy of Science USA. 84:1987;8360-8364
3. Cowman A.F., Morry M.J., Biggs B.A., Cross G.A.M., Foote S.J. Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene from Plasmodium falciparum. Proceedings of the National Academy of Science USA. 85:1988;9109-9113
4. Donald R.G.K., Roos D.S. Stable molecular transformation of Toxoplasma gondii: a selectable DHFR-TS marker based on drug-resistance mutations in malaria. Proceedings of the National Academy of Science USA. 90:1993;11703-11707
5. Elcock A.H., Potter M.J., Matthews D.A., Knighton D.R., McCammon J.A. Electrostatic channeling in the bifunctional enzyme dihydrofolate reductase-thymidylate synthase. Journal of Molecular Biology. 202:1996;370-374
6. Fox B.A., Belperron A.A., Bzik D.J. Stable transformation of Toxoplasma gondii based on a pyrimethamine resistant trifunctional dihydrofolate reductase-cytosine deaminase-thymidylate synthase gene that confers sensitivity to 5-fluorocytosine. Molecular and Biochemical Parasitology. 98:1999;93-103
7. Fox B.A., Belperron A.A., Bzik D.J. Negative selection of herpes simplex virus thymidine kinase in Toxoplasma gondii. Molecular and Biochemical Parasitology. 116:2001;85-88
8. Inselburg J., Bzik D.J., Horii T. Pyrimethamine resistant Plasmodium falciparum: overproduction of dihydrofolate reductase by a gene duplication. Molecular and Biochemical Parasitology. 26:1987;121-134
9. Inselburg J., Bzik D.J., Horii T. Three amino acid changes in the dihydrofolate reductase of a pyrimethamine-resistant mutant. Experimental Parasitology. 67:1988;361-363
10. Klepser M., Klepser T.B. Drug Treatment of HIV-related opportunistic Infections. Drugs. 53:1997;40-73
11. Knighton D.R., Kan C.C., Holand E., Janson C.A., Hostmska Z., Welsh K.M., Matthews D.A. Structure of and kinetic channeling in bifunctional dihydrofolate reductase-thymidylate synthase. Nature Structural Biology. 1:1994;186-194
12. Luft B.J., Remington J.S. Toxoplasmic encephalitis in AIDS. Clinical Infectious Diseases. 15:1992;211-222
13. O'Neil R.H., Lilien R.H., Donald B.R., Stroud R.M., Anderson A.C. Phylogenetic classification of protozoa based on the structure of the linker domain in the bifunctional enzyme, dihydrofolate reductase-thymidylate synthase. Journal of Biological Chemistry. 278:2003;52980-52987
14. Reynolds M.G., Roos D.S. A biochemical and genetic model for parasite resistance to antifolates. Journal of Biological Chemistry. 273:1998;3461-3469
15. Reynolds M.G., Oh J., Roos D.S. In vitro generation of novel pyrimethamine resistance mutations in the Toxoplasma gondii dihydrofolate reductase. Antimicrobial Agents and Chemotherapy. 45:2001;1271-1277
16. Roos D.S. Primary structure of the DHFR-TS gene from Toxoplasma gondii. Journal of Biological Chemistry. 268:1993;6269-6280
17. Sirawaraporn W., Prapunwattana P., Sirawaraporn R., Yuthavong Y., Santi D.V. The dihydrofolate reductase domain of Plasmodium falciparum thymidylate synthase-dihydrofolate reductase. Journal of Biological Chemistry. 268:1993;21637-21644
18. Sirawaraporn W., Sathitkul T., Sirawaraporn R., Yuthavong Y., Santi D.V. Antifolate-resistant mutants of Plasmodium falciparum dihydrofolate reductase. Proceedings of the National Academy of Science USA. 94:1997;1124-1129
19. Tanaka M., Gu H., Bzik D.J., Li W.B., Inselburg J. Dihydrofolate reductase mutations and chromosomal changes associated with pyrimethamine resistance of Plasmodium falciparum. Molecular and Biochemical Parasitology. 39:1990;125-132
20. Trujillo M., Donald R.G.K., Roos D.S., Greene P.J., Santi D.V. Heterologous expression and characterization of the bifunctional dihydrofolate reductase-thymidylate synthase enzyme of Toxoplasma gondii. Biochemistry. 35:1996;6366-6374
21. Yuvaniyama J., Chitnumsub P., Kamchonwongpaisan S., Vanichtanankul J., Sirawaraporn W., Taylor P., Walkinshaw M.D., Yuthavong Y. Nature Structural Biology. 10:2003;357-365