The Control of Non-Chemical Steps in Enzyme Catalysis

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Enzymes control the rate at which almost all chemistry of life occurs. They are also at the core of therapeutic intervention, industrial biotechnology, and synthetic biology, where biology is being utilised in entirely new ways. The manipulation of enzyme activity is a key element in each of these areas of research. Hence, understanding what determines the activity of enzymes is a high priority. Enzyme activity has been studied for many decades but important aspects of how they work have eluded the scientific approaches available at the time. Very recently, tools have been developed that allow the examination of enzymes at the resolution of almost every individual atom, telling us about their properties, how they interact and how they move. This opens up the opportunity to examine in far greater detail than has been possible to-date how enzymes behave at different stages of their reaction cycles. A proper understanding of all of these elements and their interplay is crucial to manipulating enzyme activity. In this study we will address three questions. Firstly we will examine why certain amino acids at specific positions in enzymes are the same in a wide variety of different organisms and yet, according to current models, have no role in how the enzymes work. Secondly, we will examine whether enzymes use tricks that sometimes occur when two proteins interact that make sure that the interaction is specific but neither strong nor long lasting. Thirdly, we will examine whether a behaviour found in some enzymes when they are in a resting phase are specifically present to ensure that the whole population of an enzyme is not too active unless the conditions are right. This scenario occurs when an enzyme does more than one job, and it is detrimental to be too fast doing one of the jobs. The overall context of the study is to develop better predictive models that improve the utilization of enzymes in therapeutic, industrial biotechnology and synthetic biology settings.