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Biochemistry seminar – Professor Kurt Krause

Undergraduate students, Postgraduate students, Staff
Event type
School of Biomedical Sciences

My laboratory is primarily devoted to the study of prominent 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. Through the years we have had projects that focussed on enzyme structure and function, enzyme regulation, drug discovery and on proteins that modulate immunity.

In this seminar two vignettes will be presented in the area of drug discovery.

The first vignette centres on a membrane protein from M. tuberculosis called bd oxidase. bd is a terminal cytochrome oxidase that may be a gateway to a rapid cure for tuberculosis. It is an integral membrane protein containing three prosthetic heme groups which shuttle electrons to reduce oxygen – speeding it on its way to become water. In solving the structure of bd oxidase we uncovered three surprises that I will detail, as they have impacted how we believe bd functions mechanistically.

The second vignette 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 only to find that the enzyme is essentially "dead" in its natural or "unliganded" state. However, I will share what we have learned from studies we carried out with a remarkable allosteric activator of glutamate racemase which reorganises this enzyme's exterior and accelerates its speed by five orders of magnitude.

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Department of Biochemistry


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