Work carried out as part of our collaboration with Dr Ross Anderson in the School of Biochemistry was published in Nature Communications this week. The Anderson group use a bottom up approach to design functionality into simple protein scaffolds. In this publication they report an artificial enzyme that can outperform the natural version in some cases. The enzyme is an efficient heme peroxidase that catalyzes a diverse array of substrate oxidations coupled to the reduction of H2O2.
In the university press release Ross explained “We describe these proteins as maquettes, a term used in sculpture to denote a scale model from which a final work is created.” “The protein maquette similarly allows the designer to incorporate functional elements onto a stable protein scaffold. In this case, we adapted an earlier maquette design where we used the machinery present in a living bacterial cell to permanently graft the heme molecule into the protein’s structure.”
Jonathan Jenkins who is supervised by both Ross Anderson and Adrian Mulholland carried out a portion of the experimental work as well as the computational calculations. These included molecular dynamics and substrate docking studies (using Bristol University’s Docking Engine, BUDE) with assistance from Dr Richard Sessions. The docking simulations strongly identified a possible substrate binding pocket which can now be further characterized and experimentally validated.
‘Construction and in vivo assembly of a catalytically proficient and hyperthermostable de novo enzyme’ by D. Watkins, J. Jenkins, K. Grayson, N. Wood, Jack. Steventon, K. Le Vay, M. Goodwin, A. Mullen, H. Bailey, M. Crump, F. MacMillan, A. Mulholland, G. Cameron, R. Sessions, S. Mann & J. L. Ross Anderson in Nature Communications