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

Kai Zhang, Pradipsinh K Rathod

Science (New York, N.Y.) 2002 Apr 19

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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.

Citation

Kai Zhang, Pradipsinh K Rathod. Divergent regulation of dihydrofolate reductase between malaria parasite and human host. Science (New York, N.Y.). 2002 Apr 19;296(5567):545-7