Specificity in protein-carbohydrate recognition

The recognition of carbohydrates by proteins is a critical aspect of the ch emistry of biological systems. Carbohydrates can be covalently attached to either glycolipids or glycoproteins where they form a class of molecules wh ich are required in biological processes such as cell adhesion, inflammatio n, differentiation, development, and intercellular communication. In additi on, glycoconjugates frequently serve as receptors for the attachment of bac teria, viruses and toxins to cell surfaces. The two classes of proteins inv olved 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 fun damental basis for specificity of protein-carbohydrate interactions is the complementary nature of the carbohydrate substrate or receptor to its combi ning site on the protein; however, specificity can be modified by factors b oth inside and outside of the combining site. Site-directed mutagenesis stu dies on enzymes are yielding direct insights to the mechanisms of carbohydr ate recognition. In particular, studies of the glycosyltransferase enzymes which confer human major blood group determinants reveal that substrate rec ognition does not proceed with complete specificity, even in the synthesis of biologically important structures like the A and B blood group trisaccha ride antigens. Further, these studies show how single point mutation of an amino acid residue in the enzyme structure can substantially alter oligosac charide substrate usage. Once formed by glycosyltransferases and other enzy mes, many glycoconjugates act as receptors for a variety of carbohydrate-bi nding proteins, where an absence of absolute substrate specificity is also observed. Interestingly, a number of carbohydrate-binding antibodies have b een reported in which complementarity alone is not sufficient to distinguis h their target oliogosaccharide, and which utilize molecular mechanisms ext ernal to the combining site to achieve effective recognition. These antibod ies bind with a high degree of specificity and recognize their target glyco conjugate not only by its complementarity to the combining site, but also b y the cellular context in which the carbohydrate molecule is presented.