Uncovering the Relationship between Sulphation Patterns and Conformation of Iduronic Acid in Heparan Sulphate

The L-iduronic acid (IdoA) residue is a critically important structural component in heparan sulphate polysaccharide for the biological functions. The pyranose ring of IdoA is present in (1)C(4)-chair, (2)S(O)-skew boat, and less frequently, in (4)C(1)-chair conformations. Here, we analyzed the conformation of IdoA residue in eight hexasaccharides by NMR. The data demonstrate a correlation between the conformation of IdoA and sulphations in the surrounding saccharide residues. For the 2-O-sulpho IdoA residue, a high degree of sulphation on neighboring residues drives ring dynamics towards the (2)S(O)-skew boat conformer. In contrast, the nonsulphated IdoA residue is pushed towards the (1)C(4)-chair conformer when the neighboring residues are highly sulphated. Our data suggest that the conformation of IdoA is regulated by the sulphation pattern of nearby saccharides that is genetically controlled by the heparan sulphate biosynthetic pathway.