B04 - Controlling PCET and Radical Transformations in enzyme catalysis

Enzymes as the catalysts of nature constitute the chemical basis of life. A remarkable feature of enzymes is their ability to form radical intermediates, which are extremely reactive species but undergo selective transformations at ambient conditions. Radical catalysis often involves proton-coupled electron transfer (PCET) as critical steps of the pathway. This project aims to decipher fundamental principles i) of long-range PCET (through space vs. through bonds) in proteins, ii) of selective coupling of PCET with redox transformations, and iii) of reaction specificity involving reactive radical intermediates in coupled multi-step ECEC reactions. This will be achieved through a combination of state-of-the-art theoretical and experimental approaches to study the mechanism and structure of the enzyme pyruvate oxidase. One position will be opened in the Mata group and study the mechanism by computational analysis including QM/MM and MD simulations. One position will be opened in the Tittmann group with a focus on protein structure analysis by protein crystallography and functional analysis by different biophysical and biochemical tools.