Differential effect of 1,10-phenanthroline on mammalian, yeast, and parasite glycosylphosphatidylinositol anchor synthesis

Daniel Sevlever, Karl J. Mann, M. Edward Medof

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Glycosylphosphatidylinositol (GPI) anchoring of proteins to the plasma membrane is a common mechanism utilized by all eukaryotes including mammals, yeast, and the Trypanosoma brucei parasite. We have previously shown that in mammals phenanthroline (PNT) blocks the attachment of phosphoethanolamine (P-EthN) groups to mannose residues in GPI anchor intermediates, thus preventing the synthesis of mammalian GPI anchors. Therefore, PNT is likely to inhibit GPI-phosphoethanolamine transferases (GPI-PETs). Here we report that in yeast, PNT also inhibits the synthesis of the GPI anchor as well as GPI-anchored proteins. Interestingly, the mechanism of PNT inhibition of GPI synthesis is different from that of YW3548, another putative GPI-PET inhibitor. In contrast to mammals and yeast, the synthesis of GPIs in T. brucei is not affected by PNT. Our results indicate that the T. brucei GPI-PET could be a potential target for antiparasitic drugs.

Original languageEnglish (US)
Pages (from-to)1112-1118
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume288
Issue number5
DOIs
StatePublished - Nov 16 2001

Keywords

  • GPIs
  • Phenanthroline
  • Phosphoethanolamine transferases
  • Trypanosoma brucei
  • YW3548
  • pmi-40

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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