My project

This study aims to get to the heart of fundamental questions that are critical to developing our understanding of how enzymes work. Manipulating enzyme activity is at the core of therapeutic intervention, industrial biotechnology, and synthetic biology. To-date, most efforts to develop our understanding of the relationship between protein structure and dynamics, and enzyme activity have focused on active site residues and transition state stabilisation. However, in order for an enzyme to be effective, it has to do much more than preferentially bind the transition state for the reaction. As a minimum, it has to bind and release the substrate(s) and product(s) with appropriate affinities and rates, and it has to set up and release the conformation(s) in which the chemical step occurs. What determines these stabilities and dynamics is largely unknown. Using archetypal phosphoryl transfer enzymes, we will exploit recent advances in structural biology (NMR and X-ray crystallography), biophysics and in vivo protein biochemistry to establish how these enzymes control these essential elements of catalysis.

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