Oral Presentation 2014 International Biophysics Congress

Examining the allosteric properties of key metabolic enzymes (#9)

Emily Parker 1 , Eric Lang 1 , Penel J Cross 1 , Nicola J Blackmore 1 , Wanting Jiao 1 , Ali Reza Nazmi 1
  1. Department of Chemistry and Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand

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

  1. Cross PJ, Allison TM, Dobson RCJ, Jameson GB, Parker EJ. Engineering allosteric control to an unregulated enzyme by transfer of a regulatory domain. Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 2111-2116.
  2. Cross PJ, Dobson RCJ, Patchett ML, Parker EJ. Tyrosine latching of a regulatory gate affords allosteric control of aromatic amino acid biosynthesis. J. Biol. Chem. 2011, 286, 10216-10224.
  3. Blackmore NJ, Reichau S, Jiao W, Hutton RD, Baker EN, Jameson GB, Parker EJ. Three sites and you are out: Ternary synergistic allostery controls aromatic amino acid biosynthesis in Mycobacterium tuberculosis. J. Mol. Biol. 2013, 425, 1582-1592.