This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hekmat-Nejad, M. Articles by Rathod, P. K. Search for Related Content PubMed PubMed Citation Articles by Hekmat-Nejad, M. Articles by Rathod, P. K.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, 07 1996, 1628-1632, Vol 40, No. 7
Copyright © 1996 by the American Society for Microbiology. All rights reserved.

Kinetics of Plasmodium falciparum thymidylate synthase: interactions with high-affinity metabolites of 5-fluoroorotate and D1694

M Hekmat-Nejad and PK Rathod
Department of Biology, Catholic University of America, Washington, D.C. 20064, USA.

Consistent with a proposed mechanism for the potent antimalarial activity of 5-fluoroorotate, 5-fluoro-2'-deoxyuridylate inhibited Plasmodium falciparum thymidylate synthase with a Ki of 2 nM. Steady- state kinetics revealed no significant differences between malarial and mammalian thymidylate synthases. Thus, additional biochemical parameters must underlie the selective antimalarial activity of 5- fluoroorotate. A polyglutamylated folate analog, D1694-(glu)4, was also a potent inhibitor of malarial thymidylate synthase (Kis = 1.5 nM).

This article has been cited by other articles:

• Aboge, G. O., Jia, H., Terkawi, M. A., Goo, Y.-K., Nishikawa, Y., Sunaga, F., Namikawa, K., Tsuji, N., Igarashi, I., Suzuki, H., Fujisaki, K., Xuan, X. (2008). Cloning, Expression, and Characterization of Babesia gibsoni Dihydrofolate Reductase-Thymidylate Synthase: Inhibitory Effect of Antifolates on Its Catalytic Activity and Parasite Proliferation. Antimicrob. Agents Chemother. 52: 4072-4080 [Abstract] [Full Text]  
• Zhang, K., Rathod, P. K. (2002). Divergent Regulation of Dihydrofolate Reductase Between Malaria Parasite and Human Host. Science 296: 545-547 [Abstract] [Full Text]  
• Jiang, L., Lee, P.-C., White, J., Rathod, P. K. (2000). Potent and Selective Activity of a Combination of Thymidine and 1843U89, a Folate-Based Thymidylate Synthase Inhibitor, against Plasmodium falciparum. Antimicrob. Agents Chemother. 44: 1047-1050 [Abstract] [Full Text]  
• Shallom, S., Zhang, K., Jiang, L., Rathod, P. K. (1999). Essential Protein-Protein Interactions between Plasmodium falciparum Thymidylate Synthase and Dihydrofolate Reductase Domains. J. Biol. Chem. 274: 37781-37786 [Abstract] [Full Text]  
• Rathod, P. K., McErlean, T., Lee, P.-C. (1997). Variations in frequencies of drug resistance in Plasmodium falciparum. Proc. Natl. Acad. Sci. USA 94: 9389-9393 [Abstract] [Full Text]