Glutamate racemase is an essential protein in the pathogenic bacterium, Pseudomonas aeruginosa. Widespread antibiotic resistance in Pseudomonas has put this bacterium on the World Health Organization’s top 5 list for new antibiotic development. We targeted glutamate racemase as part of a drug discovery project only to find that the enzyme, when purified in vitro, is essentially "dead" in its natural or "unliganded" state. However, when complexed with a cell wall precursor, UDP-N-acetylmuramate-L-Ala, its enzyme activity accelerates by four orders of magnitude and substrate affinity improves more than 10-fold. High-resolution structural studies in the presence and absence of this allosteric activator, the first for this enzyme, detail extensive electrostatic remodelling of the enzyme’s surface to accommodate activator binding. These changes propagate through the enzyme into the active site and have provided clear hypotheses concerning enzyme activation. In addition, analysis of the molecular details of activator binding have allowed us to develop a sequence based predictive binding model. These details will enhance drug target development for this enzyme and accelerate drug discovery research.