Professor Gideon Davies

01904 328260
Email: davies@ysbl.york.ac.uk

Structural Enzymology and Carbohydrate Chemistry

Career Summary

Following a PhD at the University of Bristol with Herman Watson (X-ray crystallography) and Len Hall (molecular biology) Gideon Davies first moved to the European Molecular Biology Laboratory (EMBL) Hamburg synchrotron outstation to work with Keith Wilson and then to the University of York to work with Dale Wigley on the structure of DNA gyrase. Gideon Davies remained in York, incorporating extended "research leave" periods in Hamburg, Grenoble and Uppsala, and returned full time to York in 1996 through the provision of a Royal Society University Research Fellowship. In 2000, he spent a year as the "Peter Wall Catalytic Visitor" of the University of British Columbia to work on novel chemoenzymatic methods in organic synthesis and to unravel the "textbook" mechanism of lysozyme with Steve Withers. Gideon was made a full professor of the University of York in 2001 and appointed as one of the Universities "40th Anniversary Professors" in 2004.  Davies has received a number of academic awards including the 1998 “Dextra” Carbohydrate Research Award of the Royal Society of Chemistry, the 2001 Corday-Morgan Medal of the same organisation and the Roy L Whistler award of the International Carbohydrate Organisation in 2006. In December 2006 Davies received a Royal Society-Wolfson Research Merit award. In 2008, Davies was awarded the Royal Society of Chemistry Peptides and Proteins Medal.

Research Summary

Research in the Davies group (see our group web pages) is focused on the structural enzymology and biological chemistry of the enzymes, and their accessory domains, that are involved in the synthesis, modification and breakdown of carbohydrates.  One of the group’s main themes is the analysis of the conformational pathways harnessed by enzymes. A feature has been the description of conformational changes along the reaction coordinate and insight into roles of pyranoside ring distortion in glycoside hydrolysis: the 1 S 3 skew-boat Michaelis complex, the 2,5 B intermediate in xylan degradation. Recent work (Ducros et al, 2002, Angew Chemie Int Ed; Money et al, 2006 Angew Chemie Int Ed) points to the 1 S 5 Michaelis and B 2,5 transition-state in β-mannoside hydrolysis and in 2001 working with Steve Withers at UBC we unveiled the covalent intermediate during the catalytic cycle of lysozyme (Vocadlo et al, 2001, Nature). This work is now impacting on the design of new inhibitors and drugs. The group also has major research programmes on the Chemistry of the O-GlcNAc modification of higher eukaryotes (see for example Dennis et al, 2006 Nature Struct Mol Biol; Whitworth et al, 2006 J Am Chem Soc in press) and on glycosyltransferases: Natures synthetic apparatus for carbohydrate synthesis (see for example Flint et al, 2005 Nature Struct Mol Biol; Offen et al, 2006 EMBO Journal).

Snapshots along the reaction pathway Graphic of O-GlcNAcase Macrolide structure

Selected Recent Publications

  • A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo.
    S A Yuzwa, M S Macauley, J E Heinonen, X Shan, R J Dennis, Y He, G E Whitworth, K A Stubbs, E J McEachern, G J Davies and D J Vocadlo, 2008, Nature Chemical Biology, 4, 483-490.
  • Mechanistic Insights into Glycosidase Chemistry.
    D Vocadlo and G J Davies, 2008, Curr Opin Chem Biol, 12, 539-555.
  • Structure of an O-GlcNAc transferase homolog provides insight into intracellular glycosylation.
    C Martinez-Fleites, M S Macauley, Y He, D L Shen, D J Vocadlo and G J Davies, 2008, Nature Struct Mol Biol, 15, 764-765.
  • Structural and biochemical evidence for a boat-like transition state in ß-mannosidases.
    L N Tailford, W A Offen, N L Smith, C Dumon, C Morland, J Gratien, M-P Heck, R V Stick, Y Blériot, A Vasella, H J Gilbert and G J Davies, 2008, Nature Chem Biol, 4, 306-312.