Fucosyltransferases in Schistosoma mansoni development

E. T.A. Marques, Y. Ichikawa, M. Strand, J. T. August, G. W. Hart, R. L. Schnaar

Research output: Contribution to journalArticlepeer-review

Abstract

Glycoconjugate-bound fucose, abundant in the parasite Schistosoma mansoni, has been found in the form of Fucα1,3GlcNAc, Fucα1,2Fuc, Fucα1,6GlcNAc, and perhaps Fucα1,4GlcNAc linkages. Here we quantify fucosyltransferase activities in three developmental stages of S. mansoni. Assays were performed using fluorophore-assisted carbohydrate electrophoresis with detection of radioactive fucose incorporation from GDP-[14C]-fucose into structurally defined acceptors. The total fucosyltransferase-specific activity in egg extracts was 50-fold higher than that in the other life stages tested (cercaria and adult worms). A fucosyltransferase was detected that transferred fucose to type-2 oligosaccharides (Galβ1,4GlcNAc-R), both sialylated (with the sialic acid attached to the terminal Gal by α2,3 or 2,6 linkage) and nonsialylated. Another fucosyltransferase was identified that transferred fucose to lactose-based and type-2 fucosylated oligosaccharides, such as LNFIII (Galβ1,4(Fucα1,3)GlcNAcβ1,3Galβ1,4Glc). A low level of fucosyltransferase that transfers fucose to nosialylated type-1 oligosaccharides (Galβ1,3GlcNAc-R) was also detected. These studies revealed multifucosylated products of the reactions. In addition, the effects of fucose-type iminosugars inhibitors were tested on schistosome fucosyltransferases. A new fucose-type 1-N-iminosugar was four- to six fold more potent as an inhibitor of schistosome fucosyltransferases in vitro than was deoxyfuconojirimycin. In vivo, this novel 1-iminosugar blocked the expression of a fucosylated epitope (mAb 128C3/3 antigen) that is associated with the pathogenesis of schistosomiasis.

Original languageEnglish (US)
Pages (from-to)249-259
Number of pages11
JournalGlycobiology
Volume11
Issue number3
DOIs
StatePublished - Mar 2001

Keywords

  • FACE
  • Fucose
  • Glycosyltransferase
  • Iminosugar
  • Schistosome
  • Trematode

ASJC Scopus subject areas

  • Biochemistry

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