Influence of saccharide modifications on heparin lyase III substrate specificities

A library of 23 synthetic heparan sulfate (HS) oligosaccharides, varying in chain length, types, and positions of modifications, was used to analyze the substrate specificities of heparin lyase III enzymes from both Flavobacterium heparinum and Bacteroides eggerthii. The influence of specific modifications, including N-substitution, 2-O sulfation, 6-O sulfation, and 3-O sulfation on lyase III digestion was examined systematically. It was demonstrated that lyase III from both sources can completely digest oligosaccharides lacking O-sulfates. 2-O Sulfation completely blocked cleavage at the corresponding site; 6-O and 3-O sulfation on glucosamine residues inhibited enzyme activity. We also observed that there are differences in substrate specificities between the two lyase III enzymes for highly sulfated oligosaccharides. These findings will facilitate obtaining and analyzing the functional sulfated domains from large HS polymer, to better understand their structure/function relationships in biological processes.

Automated summary

A library of synthetic heparan sulfate oligosaccharides was used to analyze the substrate specificities of heparin lyase III enzymes from two different sources. The study found that specific modifications influenced the digestion of the oligosaccharides, and there were differences in substrate specificities between the two lyase III enzymes for highly sulfated oligosaccharides. These findings provide insights into the structure/function relationships of sulfated domains in biological processes.