Hyaluronic acid: Structure of a fully extended 3-fold helical sodium salt and comparison with the less extended 4-fold helical forms

The structure of sodium hyaluronate packed in a trigonal lattice ( a = b = 1·17 nm, c (fiber axis) = 2·850 nm, γ = 120°) has been determined and refined against X-ray diffraction data and a quadratic approximation to non-bonded repulsion. The polysaccharide chain is a regular, left-handed 3-fold helix stabilized by O --- O intramolecular hydrogen bonds across the two kinds of glycosidic linkage. The hydroxymethyl side chain is oriented approximately gauche-gauche and the plane of the acetamido side chain is approximately normal to the helix axis. Two such chains pass through the unit cell in opposite directions intersecting the base plane at ( x f = 2/3, y f = 1/3) and ( x f = 1/3, y f = 2/3). The two chains are related by the dyad axis symmetry of the space group, P3 221. Each carboxylate group is bound to one sodium ion which in turn binds to two oxygen atoms from a second polyanion chain and three water molecules. One of these water molecules is located in a crystallographic special position on the x,x,0 dyad and is therefore shared by two Na + co-ordination shells. Most of the inter-chain hydrogen bonding involves water bridges and there is no direct bonding between acetamido side chains. The structure is compared to other forms of hyaluronic acid and the consequences of the different forms of intermolecular associations are considered in detail.