Influence of L-fucose attached alpha 1->6 to the asparagine-linked N-acetylglucosamine on the hydrolysis of the N-glycosidic linkage by human glycosylasparaginase

被引:18
作者
Noronkoski, T [1 ]
Mononen, I [1 ]
机构
[1] KUOPIO UNIV HOSP,DEPT CLIN CHEM,FIN-70211 KUOPIO,FINLAND
关键词
aspartylglucosaminidase; fucosidosis; glycoprotein degradation; glycosylasparaginase; lysosomal enzymes;
D O I
10.1093/glycob/7.2.217
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The sequence of hydrolytic reactions in the catabolism of the N-glycosidic oligosaccharide-to-protein region containing 6-linked fucose on the asparagine-linked N-acetylglucosamine may vary from species to species, When alpha-L-fucopyranosyl-(1-->6)-2-acetamido-1-N-(beta-L-aspartyl)-2-deoxy-beta-D-glucopyranosylamine (Fuc-GlcNAc-Asn) was incubated with recombinant human glycosylasparaginase, no hydrolysis of the N-glycosidic bond was detected, After removal of the alpha 1-->6-linked fucose from the compound by alpha-fucosidase, the residual GlcNAc-Asn was rapidly hydrolyzed by glycosylasparaginase. Enzymologically this demonstrates for the first time that the catabolism of Fuc-GlcNAc-Asn in humans occurs via consecutive action of alpha-fucosidase and glycosylasparaginase. The hydrolysis rate of GlcNAc-Asn by glycosylasparaginase remained unaffected in the presence of Fuc-GlcNAc-Asn or several different monosaccharides including fucose. This indicates that any fucose attached (alpha 1-->6 to the asparagine-linked N-acetylglucosamine residue prevents the access of the L-asparagine residue of Fuc-GlcNAc-Asn into the deep, funnel-shaped active site of human glycosylasparaginase. These findings explain the accumulation of fucosylated and normal catabolism of nonfucosylated glycoasparagines in fucosidosis.
引用
收藏
页码:217 / 220
页数:4
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