Reversible modification of methionine as a mechanism to regualte protein function in the mitochondrion and secretory pathway

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The function of cells and tissues is often regulated by proteins that can be switched on or off by their reversible modification. These cellular function include critical processes such as cell-division, metabolism and death so it is important that we understand how these reversible modifications occur. This project aims to study one type of poorly characterised modification, called methionine oxidation, which can occur during conditions of cell stress. Specifically we will gain detailed information on the ability of a specific enzyme to catalyse both the oxidation and reduction of proteins - essentially being able to switch on and off protein function. Hence, the research has the potential to unravel a key mechanism for regulating cellular function during normal physiology and during stress.To understand this enzyme more fully, we will determine its 3-dimensional structure during its catalytic cycle and in that way obtain a detailed understanding of how it works. We will also develop new chemical probes which will enable us to follow its enzymatic activity within live cells providing unprecedented detail on its location and activity under normal and stress conditions. Finally, we will use our knowledge of the enzyme's mechanism to identify the substrates of the enzyme, in other words, the proteins it is able to turn on and off. Using this information we will understand how, where and when the enzyme works and unravel the cellular functions that are controlled by its activity.