Professor David Rice
School of Biosciences
+44 114 222 4242
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School of Biosciences
- 2008 - 2020: Harrison Chair in Structural Biology, University of Sheffield
- 1996 - 2007: Chairman of the Department of Molecular Biology and Biotechnology, University of Sheffield
- 1993 - 2007: Director of the Krebs Institute for Biomolecular Research, University of Sheffield
- 1990: Visiting Professor - Dept. of Biochemistry and Biophysics Washington State University, USA
- 1988 - 93: Research Fellow of the Lister Institute of Preventive Medicine, University of Sheffield
- 1984 - 87: Science and Engineering Research Council Special Replacement Lecturer, University of Sheffield
- 1987: Visiting Lecturer - Dept. of Chemistry and Biochemistry Massey University, New Zealand.
- 1981 - 84: Independent Research Worker, University of Sheffield.
- 1979 - 81: Postdoc, Laboratory of Molecular Biophysics, Oxford
- 1979: D.Phil., St. Catherine's College, Oxford 'X-ray crystallographic studies on the sequence, structure and activity of horse muscle phosphoglycerate kinase'
- 1971 - 75: B.A. Honours Chemistry, St. Catherine's College, Oxford
Honours and Distinctions
- 1997: Awarded a Wellcome visiting Professorship in Basic Medical Sciences at the University of Maryland, USA
- 1988 - 93: Awarded a Research Fellowship of the Lister Institute of Preventive Medicine
- 1984 - 87: Awarded a Science and Engineering Research Council Special Replacement Lectureship
- 1980 - 81: Elected to a Junior Research Fellowship, Linacre College, Oxford
- Research interests
My laboratory is concerned with the use of X-ray crystallography to determine structure/function relationships in proteins. Such studies provide a powerful route towards understanding basic biological mechanisms, contribute towards the rational design of new drugs and underpin the use of enzymes for industrial and biomedical applications.
A major programme in the laboratory concerns progress towards the design of novel herbicides and a recent highlight includes the structure determination of A. thaliana imidazoleglycerol-phosphate dehydratase, an enzyme of histidine biosynthesis and a target for the experimental family of triazole phosphonate herbicides.
The structure is composed of twenty-four identical subunits arranged in 432 symmetry and shows how the formation of a novel dimanganese cluster is crucial to the assembly of the active 24mer from an inactive trimeric precursor and to the formation of the active site of the enzyme.
Molecular modelling suggests that the substrate is bound to the manganese cluster as an imidazolate moiety (Fig 1b) which subsequently collapses to yield a diazafulvene intermediate.
The mode of imidazolate recognition exploits pseudo-symmetry at the active site arising from a combination of the assembly of the particle and pseudo-symmetry present in each subunit as a result of gene duplication.
This provides an intriguing example of the role of evolution in the design of Nature’s catalysts and has opened up the opportunity of analysing the mode of inhibitor binding as a contribution towards a programme of rational herbicide design.
- Teaching activities
Level 4 Modules
- MBB405 Advanced Research Topics
Level 3 Modules
- MBB302 Physical Methods for Studying Biological Structures (Module Coordinator)
- MBB362 Biochemistry Data Handling
Level 2 Modules
- MBB261 Biochemistry 2
- MBB265 Practical Molecular Bioscience 2
- MBB266 Biostructures, Energetics and Synthesis