Poster Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

Dihydrodipicolinate synthase is allosterically regulated via a water channel. (#111)

Amanda Board 1 , Renwick Dobson 1 2
  1. University of Canterbury, Christchurch, CANTERBURY, New Zealand
  2. Bio21 Institute, University of Melbourne, Melbourne, Victoria, Australia

Dihydrodipicolonate synthase (DHDPS) is a protein found in plants and bacteria that catalyses the first committed step of the lysine biosynthesis pathway. This work will test the importance of a water channel that connects the allosteric and catalytic sites of the enzyme. The theory is that the water channel is needed for catalysis and is involved in the allosteric mechanism. In this study mutants will be made to block said channel with bulky amino acid residues. Kinetic studies and X-ray crystallography will be performed on the mutants and they will be compared to the wild type. As DHDPS is only found in bacteria and plants and not humans, it presents a useful antibiotic target. Recently work has been done on developing an antibiotic that blocks the function via the allosteric site. If DHDPS is inactivated then the organism cannot produce lysine and will die. This work will help further the work on developing inhibitors and potential antibiotics.