[Seminar] "Adventures in academic drug discovery with a focus on Pseudomonas aeruginosa" by Prof. Kurt Krause

Speaker: Prof. Kurt Krause,  University of Otago, Department of Biochemistry

Title: Adventures in academic drug discovery with a focus on Pseudomonas aeruginosa

Abstract:

My laboratory is primarily devoted to the study of vital proteins involved in infectious diseases. Our goal is to figure out how these proteins are used by pathogens to help bring about disease and to see if the proteins have a weak point that can be pinpointed and exploited. In our work, we have studied enzyme structure and function, enzyme regulation, drug discovery,  and even how some proteins are able to modulate human immunity. 
 
In this seminar I will provide a short lab overview followed by a vignette that centres on glutamate racemase, an essential protein in the pathogenic bacterium, Pseudomonas aeruginosa. Widespread antibiotic resistance in Pseudomonas has put this bacterium on WHO's top 5 list for new antibiotic development. We targeted glutamate racemase as part of a drug discovery project, because it had been shown to be essential. But in our initial studies we were surprised to find that the enzyme is essentially "dead" in its natural or "unliganded" state. However, I will share what we have learned from studies carried out with a remarkable allosteric-site activator which reorganises this enzyme's exterior and accelerates its speed by five orders of magnitude.