Figure 1. Glycosyltransferase (GT) folds and mechanisms.
Top: The three representative structural folds of GTs. The GT-A fold is characterized by a single globular domain that contains a α/β/α Rossmann nucleotide binding domain (shown 2rj7;GT6). The GT-B fold enzymes are usually metal independent and contain two α/β/α domains separated by a flexible linker region with the substrate binding cleft in between (shown 1jg7;GT63). The GT-C fold enzymes are hydrophobic integral membrane proteins, generally use lipid phosphate linked sugar donors and have multiple transmembrane helices (shown 6gxc; GT66). Bottom: The mechanism of sugar transfer employed by GTs. Inverting GTs follow a direct displacement SN-2-like mechanism that results in an inverted anomeric configuration. The mechanism for retaining GTs is still under debate although recently a same side SNi-type reaction has been proposed where the donor phosphate oxygen acts as a catalytic base and deprotonates the acceptor hydroxyl facilitating a same side attack, that results in the retention of anomeric configuration. The enzyme and catalytic base B are shown in orange. A generic hexose with α-linkage to a nucleoside diphosphate is used. Other mechanisms possibly employed by GTs is discussed in detail in M.