TERTIARY STRUCTURE OF GANGLIOSIDE G(A1) DETERMINED BY NMR-SPECTROSCOPY

Investigation of the structure of the gangliosides has proven to be ve ry important in the understanding of their biological roles. We have d etermined the tertiary structure of asialoganglioside G(M1) (G(A1)) us ing NMR spectroscopy and distance geometry calculations. All of the st ructures are very similar except the glycosidic torsion angles in the ring IV and ring III linkages. There are two low-energy structures for GA1, G1 and G2. G1 differs from G2 only in the IV-III glycosidic link ages and the orientation of acetamido group in ring III. There is a st able intramolecular hydrogen bond between the third hydroxyl group in ring I and the ring oxygen atom in ring II. Also, there may be a weak hydrogen bond between the second hydroxyl group in ring IV and the ace tamido group in ring III. Small coupling constants of (3)J(IH3,IOH3) a nd (3)J(IVH2,IVOH2) support this result. Overall structural features o f G(A1) are very similar to those of G(M1). It implicates that specifi cities of the sugar moieties in G(M1) are caused not by their tertiary foldings, but mainly by the electrostatic interactions between the po lar sialic acid and its receptors. Since it is evident that G(A1) is m ore hydrophobic than G(M1), a receptor with a hydrophobic binding site can recognize the G(A1) better than G(M1). Studies on the conformatio nal properties of G(A1) may lead to a better understanding of the mole cular basis of its functions.