Protein conformational changes and dynamics play critical roles in delivering complex enzyme function. We have examined the roles of conformational adjustments in delivering both catalysis and allosteric functionality to enzymes that play key roles in amino acid biosynthesis.
Our studies examine both the active site chemistry and allosteric regulation of ATP phosphoribosyltransferase and 3-deoxy-D-arabino heptulosonate 7-phosphate synthase. These are both enzymes that catalyse the first steps in the pathways towards the essential amino acids histidine and the aromatic amino acids respectively. Both enzymes are critical for bacterial function and have been identified as targets for antimicrobial drug design. We have examined both catalytic and allosteric mechanisms using a range of computational, kinetic and structural techniques. Our studies give insight into signal transduction, reaction mechanisms, complex formation and enzyme evolution for these two protein families.