Formation of Tyrosine Radicals in haem proteins: their role in electron transfer

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Many enzymes use highly reactive free radicals to perform their catalytic functions. Free radicals are compounds containing unpaired electrons and play an important role in a number of biological processes, many of which are necessary to sustain life. However, because of their high reactivity free radicals can also participate in unwanted side reactions, causing cell damage that may lead to many diseases including arthritis, Alzheimer's disease and cancer. Some enzymes require that free radicals are moved over large distances, whereas some require that free radicals do not move from their point of creation. The way in which enzymes control free radical movement is of important scientific interest. We intend to examine the ways in which radicals move through enzymes and proteins by using model proteins systems, namely myoglobin and haemoglobin, in which we can control the formation of free radicals at will. These proteins are known to form and translocate free radicals when they react with peroxides. We intend to follow the migration of these free radicals, using various direct and indirect free radical detection methods, to discover whether radical movement is mainly within the protein or is transmitted to other proteins. Also, we intend to manipulate the pathways through which these radicals migrate by re-designing parts of the protein. As the structures of these proteins are known we can use this information together with genetic methods to remove existing pathways and to create potential new ones. The information gained will be valuable in understanding the mechanisms by which proteins control radicals and will also be of importance in understanding why these processes go wrong in some proteins such as artificially designed haemoglobin-based blood substitutes.