Ligand Binding
Due to the acidic nature of sialic acid, Siglec active sites contain a conserved arginine residue which is positively charged at physiological pH. This amino acid forms salt bridges with the carboxyl group of the sugar residue. This is best seen in Sialoadhesin, where arginine at position 97 forms salt bridges with the COO- group of the sialic acid, producing a stable interaction. Each lectin domain is specific for the linkage that connects sialic acid to the glycan. Sialic acid contains numerous hydroxyl groups which can be involved in the formation of glycosidic linkages. Most sialic acids are bonded via the 2, 3, 6 and occasionally 8 hydroxyl groups (number dependent on the carbon to which they are attached), in an α anomeric configuration. The specificity of each Siglec is due to different chemical interactions between the sugar ligand and the Siglec amino acids. The position in space of the individual groups on the sugar and the protein amino acids affects the sialic acid linkage to which each Siglec binds. For example, Sialoadhesin preferentially binds α2,3 linkages over α2,6 linkages.
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—Milan Kundera (b. 1929)