FIGURES AND TABLES

Figure 1.

Schematic representations of type 1 and 2 Lewis carbohydrate determinants. (a) Type 1 Le^b tetrasaccharide determinant. (b) Type 2 Le^y tetrasaccharide determinant. Note that the Le^a (type 1) and Le^x (type 2) epitopes are defined by core tripeptide structures that lack the 1-2 linked Fuc residues.

Figure 2.

Antibody-bound conformations of Lewis carbohydrate determinants. The hexose rings of the GlcNAc residues were used to overlay the various ligands, namely: the Le^y tetrasaccharide from the hu3S193 Fab complex (black; 1S3K); the Le^y nonoate methyl ester (Non) from the BR96 Fab complex (black dashed lines; 1CLY); and, the Le^x (-O-methyl glycoside) trisaccharide from the 291-2G3-A Fab complex (grey; 1UZ8). This figure was prepared using the MOLMOL program⁵³

Figure 3.

Molecular surface views of antibody binding sites are displayed with bound Lewis carbohydrate ligands. The 1.9 Å resolution structure of the hu3S193 Fab complex with the Le^y tetrasaccharide (1S3K). (b) The 2.5 Å resolution structure of the BR96 Fab complex with the Le^y nonoate methyl ester (1CLY). (c) The 1.8 Å resolution structure of the 291-2G3-A Fab complex with a -O-methyl glycoside of Le^x (1UZ8). Note the almost identical shapes of the hu3S193 and BR96 binding cavities occupied by the carbohydrate portions of Le^y, and very different binding cavity and configuration of Le^x in the 291-2G3-A Fab complex. The images were prepared using Insight II (Accelrys, San Diego, USA).

Figure 4.

Role of solvent in hu3S193 binding to the Le^y tetrasaccharide. (a) Schematic diagram showing the interactions between the Le^y tetrasaccharide and binding site residues. Ordered water molecules are displayed as the larger grey spheres. Hydrogen bonding (dashed lines) and van der Waals interactions (spokes) are indicated. This figure was prepared with the LIGPLOT program⁵⁴. Molecular surface representation of hu3S193 Fab including the ordered water molecules (dark grey surfaces) surrounding the carbohydrate–protein interactions. Note the exquisite shape correspondence between the molecular surface and the bound Le^y tetrasaccharide (compare with Figure 3a).

Table 1 - Conformational characteristics of free Lewis oligosaccharides^† .