EPSRC DTP Studentship: The Link Between Efficiency and Dynamic Coupling in Enzyme Catalysis
Enzyme flexibility facilitates Michaelis complex formation and electrostatic preorganisation, yet our published work and extensive preliminary data indicate that it can be detrimental to the actual chemical transformation, as fast enzyme motions coupled to the chemical coordinate increase the frequency of unfavourable barrier recrossing events. This project aims to unravel the microscopic mechanism that couples enzyme dynamics to the chemical transformation catalysed by alcohol dehydrogenase from Geobacillus stearothermophilus (BsADH).
The extent of dynamic coupling will be investigated using isotopically labeled BsADH to assess the kinetic difference between the reactions catalysed by the ‘heavy’, isotopically labeled enzyme and ‘light’, natural abundance enzyme. In addition, the structural and electrostatic properties of the enzyme will be characterised using NMR spectroscopy of 13C- and F-labeled BsADHs in complex with different ligands, as well as with labelled ligands. The vibrational Stark effect of cyanylated BsADH-ligand complexes will also be determined to fully elucidate the electrostatic change during enzyme catalysis and its correlation with protein dynamics.
For further information and details on how to apply, see here.
We currently have several fully funded postgraduate positions available. If you are interested and highly motivated to engage in research work in a multidisciplinary group performing research at the interface between the physical and the life sciences, we would like to hear from you. These positions are open to all EU students; exceptional non-EU students are also encouraged to apply but funding arrangements will have to be made.
For further information or an informal discussion contact Professor Allemann.
Professor Rudolf K. Allemann
School of Chemistry