New challenges and opportunities in drug discovery targeting glutamate racemases

Complex biological processes necessary for life are largely conducted by enzymes. The limelight has yet to fully capture how integral and the impact enzymes play in the development of medicines. Recently, science has started to fully grasp the significance that enzyme flexibility and dynamics play in structure and function. Two case studies will be presented in this thesis in developing small molecule inhibitors for a flexible enzyme, and consequently evaluate their inhibitory mechanisms of action. Both case studies delve into inhibiting the hyper flexible enzyme, glutamate racemase. This enzyme is responsible for production of D-glutamate necessary for the cross-linking of peptidoglycan present in all bacteria. Without properly crosslinked peptidoglycan bacterial cells are subject to lysis via osmotic pressure.