Studies on the Combining Sites of Concanavalin A

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Abstract
The initial event in the biological activity of concanavalin A (Con A) involves binding of the protein to cell surface receptors. The nature and mechanism whereby such binding may occur is described in terms of cell surface carbohydrates and the demonstrated specificity of the protein. Although considerable latitude is tolerated at the C-2 position of the α-D-hexopyranose ring system, the carbohydrate binding site of Con A appears to be complementary to α-Dmannopyranosyl residues. Hapten inhibition studies indicate that each of the hydroxyl groups of this sugar is probably involved in the binding mechanism. Of the common sugars present on cell surfaces (D-glucose, D-mannose and N-acetyl-D-glucosamine), it is probably α-D-mannopyranosyl residues which react with Con A. Since the latter units are generally located in the core region of cell surface glycoproteins, it is necessary to postulate that 2-o-glycosyl-α-D mannopyranosyl units are primary receptors for Con A. Evidence supporting this view includes hapten inhibition studies with model oligosaccharides and precipitin studies with macromolecules containing internal 2-o-substituted α-D-mannopyranosyl residues. The binding to Con A of a series of oligosaccharides containing α-(l→2)-linked Dmannosyl units appears to increase up to the tetraose and then decreases; several possible explanations are considered. Acetylated Con A, although retaining its specificity, is about 50% as active as the native protein. Some biological properties of the modified protein are described. Data suggesting that Con A behaves differently in the solution phase than in the crystalline state are presented in terms of UV difference displacement studies. It is suggested that the so-called carbohydrate binding site reportedly identified in Con A crystals may not be correct.