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Science. 2002 Apr 19;296(5567):545-7.

Divergent regulation of dihydrofolate reductase between malaria parasite and human host.

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  • 1Department of Biology, The Catholic University of America, Washington, DC 20064, USA.

Erratum in

  • Science 2002 Aug 23;297(5585):1278.

Abstract

For half a century, successful antifolate therapy against Plasmodium falciparum malaria has been attributed to host-parasite differences in drug binding to dihydrofolate reductase-thymidylate synthase (DHFR-TS). Selectivity may also arise through previously unappreciated differences in regulation of this drug target. The DHFR-TS of Plasmodium binds its cognate messenger RNA (mRNA) and inhibits its own translation. However, unlike translational regulation of DHFR or TS in humans, DHFR-TS mRNA binding is not coupled to enzyme active sites. Thus, antifolate treatment does not relieve translational inhibition and parasites cannot replenish dead enzyme.

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