Introduction
Research in the Withers Group primarily focuses upon enzymes involved in glycoside cleavage and synthesis, with special emphasis upon their mechanisms. Research also focuses upon exploitation of the understandings developed. Applications range from development of new enzyme-based synthetic methodologies to new therapeutics and imaging agents. Of particular importance to this research area has been the classification of glycosidases and other carbohydrate – processing enzymes into sequence-based families by Bernard Henrissat (Marseilles). The CAZy website and the associated Wiki site CAZypedia are constant reference points and sources of inspiration.
Techniques commonly employed include:
• Synthesis of sugar-based substrates and inhibitors, particularly fluorinated sugars.
• Enzyme kinetic analysis, both steady state and pre-steady state
• Molecular Biology – cloning and expression, site-directed mutagenesis and directed evolution
• Applications of NMR to enzymology – in collaboration with Dr. Lawrence McIntosh
• Applications of mass spectrometry to enzymology using our jointly owned Q-TOF, MALDI-TOF, FT-ICR and ORBITRAP instruments
• Applications of X-ray crystallography – in collaboration with a number of crystallographers, most notably Dr. Natalie Strynadka, Dr. Gary Brayer and Dr. Gideon Davies
• High-throughput screening
Collaborators:
Austria Institute of Organic Chemistry: Arnold Stuetz and Tanja Wrodnigg
The Hospital for Sick Children / University of Toronto: Don Mahuran, Mike Tropak
Ryerson University – Toronto: Warren Wakarchuk
Simon Fraser University: Masa Niikura
University of Alberta: Michael James
University of British Columbia: Ray Andersen, Gary Brayer, Lorne Clarke, Carl Hansen, Jay Kizhakkedathu, Steve Hallam, Lawrence McIntosh, John McNeill, Natalie Strynadka, Joerg Bohlmann
University of Waterloo: David Rose
University of York: Gideon Davies