Purine import into malaria parasites as a target for antimalarial drug development

I. J. Frame, Roman Deniskin, Avish Arora, Myles H. Akabas

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Infection with Plasmodium species parasites causes malaria. Plasmodium parasites are purine auxotrophs. In all life cycle stages, they require purines for RNA and DNA synthesis and other cellular metabolic processes. Purines are imported from the host erythrocyte by equilibrative nucleoside transporters (ENTs). They are processed via purine salvage pathway enzymes to form the required purine nucleotides. The Plasmodium falciparum genome encodes four putative ENTs (PfENT1-4). Genetic, biochemical, and physiologic evidence suggest that PfENT1 is the primary purine transporter supplying the purine salvage pathway. Protein mass spectrometry shows that PfENT1 is expressed in all parasite stages. PfENT1 knockout parasites are not viable in culture at purine concentrations found in human blood (<10 μM). Thus, PfENT1 is a potential target for novel antimalarial drugs, but no PfENT1 inhibitors have been identified to test the hypothesis. Identifying inhibitors of PfENT1 is an essential step to validate PfENT1 as a potential antimalarial drug target.

Original languageEnglish (US)
Pages (from-to)19-28
Number of pages10
JournalAnnals of the New York Academy of Sciences
Volume1342
Issue number1
DOIs
StatePublished - Apr 1 2015

Keywords

  • Drug development
  • Malaria
  • Nucleoside transporter
  • Purines

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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