Project Title: Insights into enzyme catalysis through EPR spectroscopic and electrochemical methods
Summary: Respiratory complex I (NADH:ubiquinone oxidoreductase) is a vital component of the electron transport chain. Complex I is the initial site of electron input into the respiratory chain, where it acts to couple the two electron transfer from NADH to ubiquinone and the translocation of four protons across the inner mitochondrial membrane, thereby establishing the electrochemical gradient required for ATP synthesis. Although the electron transport component of complex I has been extensively studied, the actual mechanism of coupling between electron transport and proton translocation is yet to be deciphered, and therefore determination represents an intriguing and pivotal prospect in our understanding of how this enzyme assembly works
Resolving the coupling mechanism of complex I would have profound implications for the future development of therapies against mitochondrial diseases associated with complex I dysfunction. This project will aim to utilise advanced pulse EPR spectroscopic techniques to investigate the paramagnetic centres of complex I predicted to be integral to the proton pump coupling mechanism.
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