Enzyme action in glycoprotein synthesis.

Just a few decades ago, the saccharides bound to glycoproteins were considered little more than an irritation. They increased the difficulty of purifying and characterizing proteins, making proteins run as several bands on gels and smearing them on columns. They were considered a nuisance and were typically cleaved away to reveal the 'important part', the protein moiety, for structural (e.g. via X-ray crystallography or nuclear magnetic resonance) and functional studies. We now realize that that the saccharide is often as important as the protein itself, and that glycosylation can have many effects on the function, structure, physical properties and targeting of a protein. There are a myriad of reviews and books on this subject, reflecting the nearly overwhelming number of articles in print discussing saccharide structures, glycoprotein processing enzymes and the biological implication of glycosylation. This review discusses, in turn, the extent and biological relevance of glycosylation; the structures observed; how glycosylated proteins are formed in vivo; the clinical relevance of glycosylation, in terms of the correlations between disease states and unusual glycosylation patterns; and, finally, the molecules, both natural and synthetic, that can be used to study the role of carbohydrates in glycoprotein structure and function or to disrupt various carbohydrate recognition processes and enzymatic reactions in the glycoprotein synthetic pathway.