Divergent regulation of dihydrofolate reductase between malaria parasite and human host

Kai Zhang, Pradipsinh K. Rathod

Research output: Contribution to journalArticle

123 Scopus citations

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.

Original languageEnglish
Pages (from-to)545-547
Number of pages3
JournalScience
Volume296
Issue number5567
DOIs
StatePublished - Apr 19 2002

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