Investigating the Mechanism of Allosteric Control in a Crucial Biosynthetic Enzyme — ASN Events
  1. Schedule
  2. Session Seven - Poster Session B includes Happy Hour & Trade Display
  3. Investigating the Mechanism of Allosteric Control in a Crucial Biosynthetic Enzyme

Investigating the Mechanism of Allosteric Control in a Crucial Biosynthetic Enzyme (#207)

Penelope (Penel) J Cross 1 2 , Timothy M Allison 1 2 , Renwick CJ Dobson 1 2 , Geoffrey B Jameson 3 , Emily J Parker 1 2
  1. University of Canterbury, Christchurch, NZ, New Zealand
  2. Biomolecular Interaction Centre, Christchurch, NZ
  3. Massey University, Palmerston North, NZ

3-Deoxy-D-arabino-heptulosnate-7-phosphate synthase (DAH7PS) catalyses the first committed reaction towards the biosynthesis of the aromatic amino acids and many other important aromatic compounds. As this enzyme is found in microorganisms and plants, but not mammals, considerable interest has been expressed in this enzyme as a potential drug target

Different organisms adopt various strategies for the regulation of DAH7PS, however, allosteric regulation mediated by additional domains appended to the core catalytic (αβ)8 barrel is a repetitive theme. Thermotoga maritima DAH7PS (TmaDAH7PS) undergoes a significant conformational change on ligand binding whereby two ACT domains, appended to the N-terminal end of the core catalytic barrel, bind the inhibitory ligand between them.  This domain reorganisation blocks substrate access to the active site and results in inhibition of the enzyme.

This study aims to determine the interactions which define ligand specificity and probes whether the ACT domain is solely responsible for the inhibition of the enzyme.