Glycosaminoglycan Sequence Influence on Iduronate Ring Puckering

Abstract

Iduronate (IdoA) is a major monosaccharide constituent of the linear polysaccharides, called glycosaminoglycans (GAGs), that form covalent conjugates with core proteins to make proteoglycans (PGs). PGs are known as important structural components of extracellular matrix, and are increasingly recognized for their roles in cell signaling. Toward advancing understanding of the atomic-resolution structural biology of PGs, we have performed all-atom explicit-solvent molecular dynamics (MD) simulations on IdoA as a monosaccharide and in the context of oligosaccharides corresponding to fragments of the GAG dermatan sulfate (DS). The stereochemistry of the carbon atoms in the pyranose ring of IdoA and the resulting spatial distribution of functional groups attached to the ring result in a delicate thermodynamic balance between preferred ring puckering conformation for IdoA. Therefore, Cremer-Pople ring pucker analysis was applied to understand the sequence influence on IdoA in the context of DS oligosaccharide vs. IdoA monosaccharide. These results are compared with analogous simulations for glucuronate (GlcA), which is a single-site epimer (at C6) of IdoA, and makes up the related GAG chondroitin sulfate (CS).