The trimannosyl cores of N-glycans are important for the procoagulant protease-inhibitory activity of urinary protein C inhibitor

We investigated the relationship between the procoagulant protease-inhibito ry activity and the N-glycan structures in urinary protein C inhibitor (uPC I) by sequential exoglycosidase digestions based on the N-glycan structures elucidated in this report. uPCI was glycosylated on the three potential N- glycosylation sites, asparagines 230, 243 and 319 (N230, N243 and N319) in the molecule and had four biantennary complex type sugar chains. The inhibi tory activities of uPCI toward thrombin and plasma kallikrein were little c hanged by the sequential removal of N-acetylneuraminic acid and galactose r esidues from the termini and N-acetylglucosamine residues from the branches of the N-glycans. However, the inhibitory activities were markedly decreas ed by further removing alpha -mannose residues from the trimannosyl cores o f the N-glycans. These results suggest that the trimannosyl cores of N-glyc ans are important for uPCI to inhibit the procoagulant protease. (C) 2001 E lsevier Science Ltd. All rights reserved.