Abstract
Biosynthesis of mucin-type O-glycan is initiated the transfer of GalNAc which is catalyzed by pp-GalNAc-Ts. We previously cloned and characterized human pp-GalNAc-T10, which exhibited significant activity toward GalNAC-peptides but negligible activity toward non-glycosylated peptides. We determined crystal structures of this isozyme. The structure successfully explains the substrate specificity and the GalNAc position of the products. pp-GalNAc-T10 comprises two domains, catalytic and lectin domains. GalNAc-Ser are bound to only the lectin b subdomain. The distance between the catalytic center and the carbohydrate-binding site on the b subdomain influences the positions of GalNAc glycosylation on Serll-GalNAc-IgA-hinge peptide as a substrate. In addition, an alternative glyco-peptide recognition site is indicated for the reaction toward Thr4-GalNAc-IgA-hinge peptide. Two recognition modes were clearly differentiated by alanine substitutions.
