Glycobiology, 2001, Vol. 11, No. 11 945-955
© 2001 Oxford University Press
Conformation of the O-specific polysaccharide of Shigella dysenteriae type 1: molecular modeling shows a helical structure with efficient exposure of the antigenic determinant 
-L-Rhap-(1
2)--D-Galp
2Department of Medical Biochemistry and Centre for Structural Biology, University of Göteborg, Medicinaregatan 7, 405 30 Göteborg, Sweden; 3Unité de Chimie Organique, Institut Pasteur, 28 rue de Dr. Roux, 75724 Paris Cedex 15, France; 4Section on Carbohydrates, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA; and 5Department of Medical Genetics, University of Toronto, Toronto, Ontario M5S1A8, Canada
The O-specific polysaccharide of Shigella dysenteriae type 1, which has the repeating tetrasaccharide unit 
3)-
-L-Rhap-(13)--L-Rhap-(12)--D-Galp-(13)--D-GlcNAcp-(1 (A-B-C-D), is a major virulence factor, and it is believed that antibodies against this polysaccharide confer protection to the host. The conformational properties of fragments of this O-antigen were explored using systematic search with a modified HSEA method (GLYCAN) and with molecular mechanics MM3(96). The results show that the -D-Gal-(13)--D-GlcNAc linkage adopts two favored conformations, 
/
–40°/–30° (I) and 15°/30° (II), whereas the other glycosidic linkages only have a single favored / conformational range. MM3 indicates that the trisaccharide B-C-D and tetrasaccharides containing the B-C-D moiety exist as two different conformers, distinguished by the conformations I and II of the C-D linkage. For the pentasaccharide A-B-C-D-A' and longer fragments, the calculations show preference for the C-D conformation II. These results can explain previously reported nuclear magnetic resonance data. The pentasaccharide in its favored conformation II is sharply bent, with the galactose residue exposed at the vertex. This hairpin conformation of the pentasaccharide was successfully docked with the binding site of a monoclonal IgM antibody (E3707 E9) that had been homology modeled from known crystal structures. For fragments made of repetitive tetrasaccharide units, the hairpin conformation leads to a left-handed helical structure with the galactose residues protruding radially at the helix surface. This arrangement results in a pronounced exposure of the galactose and also the adjacent rhamnose in each repeating unit, which is consistent with the known role of the as -L-Rhap-(12)--D-Galp moiety as a major antigenic epitope of this O-specific polysaccharide.
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