Conformation of the branched O-specific polysaccharide of Shigella dysenteriae type 2: Molecular mechanics calculations show a compact helical structure exposing an epitope which potentially mimics galabiose Original Research Article

Conformational analyses of the branched repeating unit of the O-antigenic polysaccharide of Shigella dysenteriae type 2 have been performed with molecular mechanics MM3. A filtered systematic search on the trisaccharide α-d-GalNAc-(1→3)-[α-d-GlcNAc-(1→4)]-α-d-GalNAc forming the branch, shows essentially a single favored conformation. Also, the downstream α-d-GalNAc-(1→4)-α-d-Glc linkage is sterically constrained. The α-d-Glc-(1→4)-β-d-Gal moiety, however, forms a more flexible link region between the branch points, and shows a 90° bend similar to what is known for the galabiose moiety occurring in globo-glycolipids. The calculations indicate that consecutive repeating units in their minimum energy conformation arrange in a helical structure with three repeating units per turn. This helix is very compact and appears to be stabilized by hydrophobic interactions involving the N-acetyl groups at the branch points. Random conformational search suggests the existence of another helical structure with four repeating units per turn. It appears possible that the α-d-Glc-(1→4)-β-d-Gal moiety, which is exposed on the surface of the helical structures, can evade recognition by the immune system of the host by the mimicry of globo structures.