This research topic involves studies of biochemical molecular recognition processes, including the enzyme-catalysed non-biological reactions, the development of novel enzymes through post-translational chemical modification of enzyme active sites, and the design and development of compounds to inhibit and stimulate ion-flux through calcium ion channels.

Dienelactone hydrolase (DLH) is a bacterial enzyme which is involved in the degradation of aromatic compounds. Our primary aim was to elucidate details of the mechanism of action of the enzyme, which acts through a catalytic triad of hydrogen bonded residues at the active site.

In one mutant (C123S), Cys-123 was replaced with Ser, to produce the catalytic triad found in serine proteases. However, this mutation completely changes the catalysis displayed by the protein, from hydrolysis of the E- and Z- isomer of dienelactone by DLH to catalysis of their isomerisation by the mutant protein, dienelactone isomerase (DLI).

The properties of enzymatic catalysis have been used by chemists as the basis of artificial enzymes to increase the rate of desired reactions. Scaffolds, such as those based on cyclodextrins, are designed to bind reactants in specific way to catalyse a reaction. However, problems with these scaffolds are that they may be very difficult to synthesise or the catalysts may be inefficient. We believe existing enzymes may be used to overcome these problems. For example, by designing substrates that bind to an enzyme, a reaction that requires correct alignment and close proximity of the reacting groups may be catalysed.

The use of artificial enzymes in chemical manufacturing presents various potentially attractive methods of industrial catalysts. The scope of enzymes reactive capabilities is however extremely constrained by the existence of only 20 genetically encoded amino acids. To address this limitation, it was postulated that synthesis of artificial enzymes could be achieved through post-translational chemical modification of enzyme active site amino acid residues. This process would allow straightforward synthesis of various novel enzymes containing non-proteogenic amino acids not readily accessible through site directed mutagenesis.