Professor Gideon Davies, FRS
01904 328260
Email: gideon.davies@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 "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.
Gideon Davies has received a number of academic awards including the 1998 “Dextra” Carbohydrate Research Award of the Royal Society of Chemistry and the 2001 Corday-Morgan Medal and 2008 Peptides and Proteins Medal of the same organisation. In 2006 he received the Roy L Whistler award of the International Carbohydrate Organisation as well as a Royal Society-Wolfson Research Merit award. In 2010, he was awarded the GlaxoSmithKline award of the Biochemical Society, The Gabor Medal of the Royal Society and was elected a Fellow of the Royal Society and a member of the European Molecular Biology Organization (EMBO).
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 (recently reviewed in Davies, Planas and Rovira, Accounts Chemical Research, 2011, in press) with recent examples of our work in this area the description of the reaction pathway of α-L fucosidases (Lammerts van Bueren et al., 2010, J Am Chem Soc, 132, 1804-1806) and the O-GlcNAc hydrolase (He et al., 2010, J Am Chem Soc 132, 1807-1809). An evolving feature of our work is the development of chemical probes, based upon reaction mechanism with which to probe the biology of the cell; an example being the development (with Vocadlo, SFU) of O-GlcNAcase inhibitors as anti-Alzheimer’s compounds (Yuzwa et al., 2008 Nature Chemical Biol 4, 483-490). Major on-going projects in the laboratory include the O-GlcNAc modification, exploiting novel enzymes for biomass degradation and the bespoke synthesis of oligosaccharides, and the structural and mechanistic basis for α-mannoside enzyme chemistry (see, for example, Zhu et al., 2010, Nature Chem Biol, 6, 125-132).
Selected Recent Publications
- The Copper Active Site of CBM33 Polysaccharide Oxygenases.
G R Hemsworth et al., 2013. J Am Chem Soc. http://pubs.acs.org/doi/ipdf/10.1021/ja402106e - Structural and mechanistic insight into N-glycan processing by endo-α-mannosidase.
A J Thompson et al., Proc Natl Acad Sci (USA), 2012, 109, 781-786. - Insights into the oxidative degradation of cellulose by a copper metalloenzyme that exploits biomass components.
R J Quinlan et al., Proc Natl Acad Sci (USA), 2011, 108, 15079-15084. - Mechanistic evidence for a front-side, SNi-type reaction in a retaining glycosyltransferase.
S S Lee et al., Nature Chem Biol, 2011 7, 631–638 - Analysis of the reaction coordinate of α-L fucosidases: a combined structural and quantum mechanical approach.
A Lammerts van Bueren et al., J Am Chem Soc, 2010, 132, 1804-1806. - Visualizing the reaction coordinate of an O-GlcNAc hydrolase.
Y He et al., J Am Chem Soc, 2010, 132, 1807-1809. - A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo.
S A Yuzwa et al., Nature Chem Biol, 2008, 4, 483-490.
