The ruminant parasite Haemonchus contortus expresses an alpha1,3-fucosyltransferase capable of synthesizing the Lewis x and sialyl Lewis x antigens.
Glycoproteins from the ruminant helminthic parasite Haemonchus contortus react with Lotus tetragonolobus agglutinin and Wisteria floribunda agglutinin, which are plant lectins that recognize alpha1,3-fucosylated GlcNAc and terminal beta-GalNAc residues, respectively. However, parasite glycoconjugates are not reactive with Ricinus communis agglutinin, which binds to terminal beta-Gal, and the glycoconjugates lack the Lewis x (Le(x)) antigen or other related fucose-containing antigens, such as sialylated Le(x), Le(a), Le(b) Le(y), or H-type 1. Direct assays of parasite extracts demonstrate the presence of an alpha1,3-fucosyltransferase (alpha1,3FT) and beta1,4-N-acetylgalactosaminyltransferase (beta1,4GalNAcT), but not beta1,4-galactosyltransferase. The H. contortus alpha1,3FT can fucosylate GlcNAc residues in both lacto-N-neotetraose (LNnT) Galalpha1-->4GlcNAcbeta1-->3Galbeta1-->4Glc to form lacto-N-fucopentaose III Galbeta1-->4[Fuca1-->3]GlcNAc beta1-->3Galbeta1-4GIc, which contains the Le(x) antigen, and the acceptor lacdiNAc (LDN) GalNAcbeta1-->4GlcNAc to form GalNAc beta1-->4[Fualpha1-->3]GlcNAc. The alpha1,3FT activity towards LNnT is dependent on time, protein, and GDP-Fuc concentration with a Km 50 microM and a Vmax of 10.8 nmol-mg(-1) h(-1). The enzyme is unusually resistant to inhibition by the sulfhydryl-modifying reagent N-ethylmaleimide. The alpha1,3FT acts best with type-2 glycan acceptors (Galbeta1-->4GlcNAcbeta1-R) and can use both sialylated and non-sialylated acceptors. Thus, although in vitro the H. contortus alpha1,3FT 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.
DeBose-Boyd
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RA
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Nyame
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AK
Jasmer
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DP
Cummings
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RD
D000818:Animals; D000911:Antibodies, Monoclonal; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000276:immunology; D005033:Ethylmaleimide / Q000494:pharmacology; D005647:Fucosyltransferases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016695:Glycosyltransferases; D006189:Haemonchus / Q000201:enzymology*; D006801:Humans; D037102:Lectins; D007983:Lewis Blood Group Antigens / Q000096:biosynthesis*; D016256:Lewis X Antigen / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000096:biosynthesis*; D010940:Plant Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D012418:Ruminants / Q000469:parasitology; D000080506:Sialyl Lewis X Antigen; D013379:Substrate Specificity
D000911:Antibodies, Monoclonal; D002241:Carbohydrates; D037102:Lectins; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D009844:Oligosaccharides; D010940:Plant Proteins; D011994:Recombinant Proteins; D000080506:Sialyl Lewis X Antigen; D016695:Glycosyltransferases; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase; D005033:Ethylmaleimide