title: 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.
abstract: 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 alpha-D-GalNAc-(1-->3)-[alpha-D-GlcNAc-(1-->4)]-alpha-D-GalNAc forming the branch, shows essentially a single favored conformation. Also, the downstream alpha-D-GalNAc-(1-->4)-alpha-D-Glc linkage is sterically constrained. The alpha-D-Glc-(1-->4)-beta-D-Gal moiety, however, forms a more flexible link region between the branch points, and shows a 90 degrees 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 alpha-D-Glc-(1-->4)-beta-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.
authors.affiliation: Department of Medical Biochemistry, Centre for Structural Biology, Göteborg University, Medicinaregatan 7B, SE-405 30, Göteborg, Sweden.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Rosen
authors.forename: Armin
authors.initials: A
authors.lastname: Robobi
authors.forename: Per-Georg
authors.initials: PG
authors.lastname: Nyholm
mesh_terms: D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D039301:Computers, Molecular; D004187:Disaccharides / Q000737:chemistry* / Q000276:immunology; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D019081:O Antigens / Q000737:chemistry* / Q000276:immunology; D012762:Shigella dysenteriae / Q000737:chemistry* / Q000276:immunology; D013816:Thermodynamics
chemical_list: D004187:Disaccharides; D000939:Epitopes; D019081:O Antigens; C032103:4-O-alpha-D-galactopyranosyl-D-galactose