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

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Zhang K, Rathod PK

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

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

PubMed ID
11964483 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
PyrimethamineBifunctional dihydrofolate reductase-thymidylate synthaseProteinPlasmodium falciparum (isolate K1 / Thailand)
Yes
Inhibitor
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