Understanding the mechanism of enzyme catalysed reactions of importance in drug metabolism

The goal of this project is to understand the mechanism by which the major family of enzymes involved in drug metabolism catalyse oxidative transformations.

Such reactions are critical in both drug metabolic and biosynthetic pathways but are often poorly understood because of the difficulty of working with the enzymes and substrates involved. A better understanding their mechanism will allow one to predict and utilise their occurrence in drug metabolism, exploit such oxidations in biotechnological-based fine chemical synthesis and inhibit them in key biosynthetic pathways to develop novel chemotherapeutics.

 

Project aims

Understand the mechanism of the reactions catalysed by these enzymes. Establish the generality of the reactions and determine the structural requirements of the substrate. Work out the presence/absence and nature of intermediates via mechanistic probes.

Understand the role that the protein residues and the enzyme-substrate interactions play by: determining the substrate-bound X-ray crystal structures with compounds that undergo these reactions.

This information is combined and extended to human drug metabolising enzymes to inform the design of better drug molecules.

Supervisor

Tagged in Honours projects - Chemistry, Honours projects - Molecular & biomedical science, Honours projects - Stephen Bell, Honours projects - John Bruning