Golgi resident glycosyltransferases produce the glycoproteins essential for cell signaling, cell adhesion, tissue morphogenesis and embryonic development. Defects in glycosylation are often embryonic lethal, or result in congenital diseases like muscular dystrophphies. Despite the importance of these enzymes, there are relatively few examples of Golgi glycosyltransferase crystal structures. Until now, the bottleneck in obtaining glycosyltransferase crystals has been protein glycosylation and expression.
This project is a collaboration with Dr. Kelley Moremen' s lab at the Complex Carbohydrate Research Center. Dr. Moremen's research group has pioneered new technologies that allow the expression of soluble, homogenous glycosyltransferases. He is in the process of expressing the more than 200 glycosyltransferases in the human Gogi. For our part, we are crystallizing and solving the strutures using state-of-the-art high throughput technigues. Many of these targets will be subjected to further solution studies to dermine mechanisms, or protein engineering to create novel biochemical tools for protein tagging.