Enzymology

We explore the reaction mechanisms of cofactor dependent enzymes, with particular interest to flavo proteins, haem, cobalamin and metallo cofactor enzymes. Most of these cofactors are coloured, making them ideal candidate for detailed kinetic and spectroscopic characterisation. We apply fast reaction kinetics as well as experimental and theoretical methods to access fine details of chemical activation and dynamics. These informations will also be used to engineer these enzymes to increase the catalytic activity, efficiency, stability and to evolve them towards specialised synthetic and other biological reactions. We apply both structure-based engineering and directed evolution methods with the aim to create novel reactions of industrial importance.

Selected Publications

Menon, Binuraj R. K., Fisher, Karl, Rigby, Stephen E. J., Scrutton, Nigel S., Leys, David. 2014. A conformational sampling model for radical catalysis in pyridoxal phosphate- and cobalamin-dependent enzymes. Journal of Biological Chemistry, 289 (49), pp. 34161-34174, View
Ortmayer, Mary, Lafite, Pierre, Menon, Binuraj R. K., Tralau, Tewes, Fisher, Karl, Denkhaus, Lukas, Scrutton, Nigel S., Rigby, Stephen E. J., Munro, Andrew W., Hay, Sam, Leys, David. 2016. An oxidative N-demethylase reveals PAS transition from ubiquitous sensor to enzyme. Nature, 539 (7630), pp. 593-597, View
Menon, Binuraj R. K., Menon, Navya, Fisher, Karl, Rigby, Stephen E. J., Leys, David, Scrutton, Nigel S.. 2 015. Glutamate 338 is an electrostatic facilitator of C-Co bond breakage in a dynamic/electrostatic model of catalysis by ornithine aminomutase. FEBS Journal, 282 (7), pp. 1242-1255, View