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 language | English (US) |
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Pages (from-to) | 1112-1118 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 288 |
Issue number | 5 |
DOIs | |
State | Published - Nov 16 2001 |
Keywords
- GPIs
- Phenanthroline
- Phosphoethanolamine transferases
- Trypanosoma brucei
- YW3548
- pmi-40
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology