SCHOOL OF BIOCHEMISTRY
Research
Research groups
Research groups
Paul Race
Research Fellow
+44 (0)117 33 12150 (tel)
+44 (0)117 33 12168 (fax)
paul.race@bristol.ac.uk
Research
Crystallographic studies of a polyketide synthase associated acyltransferase
Structure function and engineering of polyketide synthases
Around two thirds of all drugs in current clinical use are derived from or based upon molecules isolated from natural sources. This constitutes a multi-billion pound global market comprising antibiotics, antifungals, antiparasitics and anticancer agents.
We are principally interested in natural products synthesised by the polyketide and related non-ribosomal peptide pathways. The group employs a range of structural (X-ray crystallography, cryo-electron microscopy, NMR and solution scattering) and functional (enzyme kinetics, spectroscopy, etc.) methods to deconvolute, at the molecular level, the catalytic mechanisms of the individual component enzymes from selected synthetic pathways. These investigations form the basis of protein engineering approaches, where we seek to manipulate pathway enzymes to yield novel derivative products with improved therapeutic activities. Current areas of major interest in the group are:
- hybrid polyketide/non-ribosomal peptide antibiotics and anticancer drugs
- polyketide based cholesterol lowering agents.
Group
Asha Nair
Recent publications
Solovyova, A.S., Pointon, J.A., Race, P.R., Kehoe, M.A. and Banfield, M.J. (2010) Solution structure of the major (Spy0128) and minor (Spy0125 and Spy0130) pili subunits from Streptococcus pyogenes. Euro. Biophys. J. Feb;39(3):469-80.
Crow, A., Race, P.R., Jubelin, G., Varela Chavez, C., Escoubas, J.M., Oswald, E., Banfield, M.J. (2009) Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei. PLoS One. 4(5):e5582.
Race, P.R., Bentley, M.L., Melvin, J.A., Crow, A., Hughes, R.K., Smith, Sessions, R.B., W., Kehoe, M., McCafferty D.G. and Banfield, M.J. (2009) Crystal structure of Streptococcus pyogenes sortase A: implications for sortase mechanism. J. Biol. Chem. Mar 13;284(11):6924-33.
Marles-Wright, J., Grant, T., Delmeau, O., van Duinen, G., Firbank S.J., Lewis, P.J., Murray, J.W., Newman, J.A., Quin, M.B., Race, P.R., Rohon, A., Tichelarr, W., van Heel, M. and Lewis, R.J. (2008) Molecular architecture of the 'stressosome', a signal integration and transduction hub. Science. Oct 3;322(5898):92-96.