Understanding enzyme catalysis

Enzymes are remarkable catalysts that can enhance the rates of chemical reactions by as much as 19 orders of magnitude, when compared with the same reaction in solution. Understanding how enzymes work is not only important for our fundamental understanding of biochemistry, but can aid the design of site selective mutations to enhance turnover and indeed teach us how to make better synthetic catalysts. Whilst a large body of work has been carried out to establish the basis of enzyme catalysis there still remain a number of unanswered questions. In particular, it is has been argued by a number of workers that it is difficult to account for the catalytic power of enzymes in terms of the stabilization of the transition state through electrostatic effects and non-covalent interactions alone. Instead, it is argued by some workers that dynamical effects (such as “vibrational gating”) and quantum-mechanical tunneling may be contributing to catalysis. Some workers have even suggested that transition state theory (TST) is not capable of accurately describing enzyme kinetics; others have argued that it is only simple transition state theory that is inadequate and more rigorous treatments are sufficient. In a collaboration with the group of Dr Colin Jackson, we are using a combination of theory and experiment to study the origin of enzyme catalysis and particularly the role of tunneling, conformational effects and electrostatic effects. 


This ARC-funded project is a collaboration with Dr Colin Jackson.