Crystal structure of an anti-carbohydrate antibody directed against Vibriocholerae 01 in complex with antigen: Molecular basis for serotype specificity

The crystal structure of the murine Fab S-20-4 from a protective anti-chole ra Ab specific for the lipopolysaccharide Ag of the Ogawa serotype has been determined in its unliganded form and in complex with synthetic fragments of the Ogawa O-specific polysaccharide (O-SP). The upstream terminal O-SP m onosaccharide is shown to be the primary antigenic determinant. Additional perosamine residues protrude outwards from the Ab surface and contribute on ly marginally to the binding affinity and specificity. A complementary wate r-excluding hydrophobic interface and five Ab-AS hydrogen bonds are crucial for carbohydrate recognition. The structure reported here explains the ser otype specificity of anti-Ogawa Abs and provides a rational basis toward th e development of a synthetic carbohydrate-based anti-cholera vaccine.