The ruminant parasite Haemonchus contortus expresses an a1,3-fucosyltransferase capable of synthesizing the Lewis x and sialyl Lewis x antigens

Russell A. DeBose-Boyd, A. Kwame Nyame, Douglas P. Jasmer, Richard D. Cummings

Research output: Contribution to journalArticle

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Abstract

Glycoproteins from the ruminant helminthic parasite Haemonchus contortus react with Lotus tetragonolobus agglutinin and Wisteria floribunda agglutinin, which are plant lectins that recognize a1,3-fucosylated GlcNAc and terminal β-GalNAc residues, respectively. However, parasite glycoconjugates are not reactive with Ricinus communis agglutinin, which binds to terminal β-Gal, and the glycoconjugates lack the Lewis x (Le(x)) antigen or other related fucose-containing antigens, such as sialylated Le(x), Lea, Leb, Le(y), or H-type 1. Direct assays of parasite extracts demonstrate the presence of an a1,3-fucosyltransferase (a1,3FT) and β1,4-N-acetylgalactosaminyltransferase (β1,4GalNAcT), but not β1,4-galactosyltransferase. The H. contortus a1,3FT can fucosylate GlcNAc residues in both lacto-N-neotetraose (LNnT) Gala1→4GlcNAcβ1→3Galβ1→4Glc to form lacto-N-fucopentaose III Galβ1→4[Fuca1→3]GlcNAcβ1→3Galβ1→4Glc, which contains the Le(x) antigen, and the acceptor lacdiNAc (LDN) GalNAcβ1→GlcNAc to form GalNAcβ1→4[Fuca1→3]GlcNAc. The a1,3FT activity towards LNnT is dependent on time, protein, and GDP-Fuc concentration with a K(m) 50 μM and a V(max) of 10.8 nmol-mg-1 h9-1). The enzyme is unusually resistant to inhibition by the sulfhydryl-modifying reagent N-ethylmaleimide. The a1,3FT acts best with type-2 glycan accepters (Galβ1→4GlcNAcβ1-R) and can use both sialylated and non-sialylated accepters. Thus, although in vitro the H. contortus a1,3FT can synthesize the Le(x) antigen, in vivo the enzyme may instead participate in synthesis of fucosylated LDN or related structures, as found in other helminths.

Original languageEnglish (US)
Pages (from-to)789-798
Number of pages10
JournalGlycoconjugate Journal
Volume15
Issue number8
DOIs
StatePublished - Dec 2 1998

Keywords

  • Haemonchus contortus
  • Le(x) antigen
  • a1,3-fucosyltransierase
  • β1,4-N-acetylgalactosaminyltransferase
  • β1,4-galactosyltransferase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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