Protein allostery, where remote ligand binding elicits a functional response, is critical to the control of metabolism. The concept of protein allostery has been described for many years, however it is only more recently that the molecular mechanisms that govern the communication between remote ligand binding sites of proteins have begun to be unravelled in detail.
We have used a combination of structural, computational and biophysical approaches to examine the allosteric function of several enzymes that operate at important control points in key biosynthetic pathways. These enzymes include the first enzyme of the shikimate pathway, 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase, and the first enzyme for the biosynthesis of histidine, ATP-phosphoribosyl transferase. We have shown significant changes in structure and/or protein dynamics are associated with the allosteric transition for these proteins. Our studies have revealed the details the molecular events that are associated with the allosteric response and shed light on the evolution of allosteric properties by enzymes.1-3