Research groups

Research

Antibiotic target aspartate semialdehyde dehydrogenase.

Proteins involved in bacterial pathogenesis.

Molecular movies for enzymes of medical and industrial importance. The best inhibitors (and therefore drugs) often mimic intermediates in enzyme mechanisms. The structure of these intermediates can be determined using substrates or substrate analogues to observe reactions in protein crystals. These structural snapshots form the basis of 'molecular movies' and can contribute to the design of novel therapeutic agents, and the adaptation of the enzymes for biosynthetic or bioremediation technologies. The techniques we employ include protein expression and purification, protein crystallography, spectroscopy (including on single crystals), enzyme kinetics, site directed mutagenesis, bioinformatics and modelling.

Group

May Marsh, Patrick Dall'Aglio

Recent publications

Hadfield, A.T., Limpkin, C., Teartasin, W., Simpson, T.J., Crosby, J., Crump, M.P. (2004) The crystal structure of the actIII actinorhodin polyketide reductase: proposed mechanism for ACP and polyketide binding. Structure 12, 1865-1875.

Teartasin, W., Limpkin, C., Glod, F., Spencer, J., Cox, R.J., Simpson, T.J., Crosby, J., Crump, M.P., Hadfield, A.T. (2004) Expression, purification and preliminary X-ray diffraction analysis of a ketoreductase from a type II polyketide synthase. Acta Crystallographica D Biological Cyrstallography 60, 1137-1138.

Cox, R.J., Hadfield, A,T., and Mayo-Martin, M.B. (2001) Difluoromethylene analogues of aspartyl phosphate: the first synthetic inhibitors of aspartate semi-aldehyde dehydrogenase. Chem Communications 21, 1710-1711.

Hadfield, A.T., Diana, G.D., and Rossmann, M.G. (1999) Analysis of three structurally related antiviral compounds in complex with human rhinovirus 16. Proceedings of the National Academy of Sciences USA 96, 14730-14735.