Specificity in Protein-Carbohydrate Recognition

Nina   O.   L.Seto; Stephen   V.   Evans

doi:10.2174/1385272003376238

Abstract

The recognition of carbohydrates by proteins is a critical aspect of the chemistry of biological systems. Carbohydrates can be covalently attached to either glycolipids or glycoproteins where they form a class of molecules which are required in biological processes such as cell adhesion, inflammation, differentiation, development, and intercellular communication. In addition, glycoconjugates frequently serve as receptors for the attachment of bacteria, viruses and toxins to cell surfaces. The two classes of proteins involved in these interactions are the enzymes which build the glycoconjugates (such as glycosyltransferases), and the proteins which recognize and bind the glycoconjugates (such as antibodies and lectins). In either case, these proteins function by recognizing specific carbohydrate structures. The fundamental basis for specificity of protein-carbohydrate interactions is the complementary nature of the carbohydrate substrate or receptor to its combining site on the protein; however, specificity can be modified by factors both inside and outside of the combining site. Site-directed mutagenesis studies on enzymes are yielding direct insights to the mechanisms of carbohydrate recognition. In particular, studies of the glycosyltransferase enzymes which confer human major blood group determinants reveal that substrate recognition does not proceed with complete specificity, even in the synthesis of biologically important structures like the A and B blood group trisaccharide antigens. Further, these studies show how single point mutation of an amino acid residue in the enzyme structure can substantially alter oligosaccharide substrate usage. Once formed by glycosyltransferases and other enzymes, many glycoconjugates act as receptors for a variety of carbohydrate-binding proteins, where an absence of absolute substrate specificity is also observed. Interestingly, a number of carbohydrate-binding antibodies have been reported in which complementarity alone is not sufficient to distinguish their target oliogosaccharide, and which utilize molecular mechanisms external to the combining site to achieve effective recognition. These antibodies bind with a high degree of specificity and recognize their target glycoconjugate not only by its complementarity to the combining site, but also by the cellular context in which the carbohydrate molecule is presented.

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