Much research has been done on glycogen degradation through studying the structure and function of glycogen phosphorylase, the key regulatory enzyme of glycogen degradation. On the other hand, much less is known about the structure of glycogen synthase, the key regulatory enzyme of glycogen synthesis. The crystal structure of glycogen synthase from Agrobacterium tumefaciens, however, has been determined at 2.3 A resolution. In its asymmetric form, glycogen synthase is found as a dimer, whose monomers are composed of two Rossmann-fold domains. This structural property, among others, is shared with related enzymes, such as glycogen phosphorylase and other glycosyltransferases of the GT-B superfamily. Nonetheless, a more recent characterization of the Saccharomyces cerevisiae (yeast) glycogen synthase crystal structure reveals that the dimers may actually interact to form a tetramer. Specifically, The inter-subunit interactions are mediated by the α15/16 helix pairs, forming allosteric sites between subunits in one combination of dimers and active sites between subunits in the other combination of dimers. Since the structure of eukaryotic glycogen synthase is highly conserved among species, glycogen synthase likely forms a tetramer in humans as well.
Glycogen synthase can be classified in two general protein families. The first family (GT3), which is from mammals and yeast, is approximately 80 kDa, uses UDP-glucose as a sugar donor, and is regulated by phosphorylation and ligand binding. The second family (GT5), which is from bacteria and plants, is approximately 50 kDA, uses ADP-glucose as a sugar donor, and is unregulated.