TY - JOUR
T1 - The ruminant parasite Haemonchus contortus expresses an a1,3-fucosyltransferase capable of synthesizing the Lewis x and sialyl Lewis x antigens
AU - DeBose-Boyd, Russell A.
AU - Nyame, A. Kwame
AU - Jasmer, Douglas P.
AU - Cummings, Richard D.
N1 - Funding Information:
This work was supported by NIH Grant AI266725 to Richard D. Cummings and USDA Grant 45-02158 to Douglas P. Jasmer. Russell A. DeBose-Boyd is supported by a National Research Service Award GM18274-02 from the NIGMS. We thank Ms. Lela Carter for assistance in preparing the manuscript.
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
KW - Haemonchus contortus
KW - Le(x) antigen
KW - a1,3-fucosyltransierase
KW - β1,4-N-acetylgalactosaminyltransferase
KW - β1,4-galactosyltransferase
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U2 - 10.1023/A:1006912032273
DO - 10.1023/A:1006912032273
M3 - Article
C2 - 9870355
AN - SCOPUS:0031789004
SN - 0282-0080
VL - 15
SP - 789
EP - 798
JO - Glycoconjugate Journal
JF - Glycoconjugate Journal
IS - 8
ER -