Enzyme catalysis of nucleophilic attack of anions by anions

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The present application aims to get to the heart of fundamental questions that are critical to developing our understanding of how enzymes work. Enzymes, which are normally proteins, control the rate at which almost all chemistry occurs in living systems. Understanding enzyme activity is a high priority - it is at the core of therapeutic intervention, industrial biotechnology, and synthetic biology. The controlled manipulation of enzyme activity is one of the key elements targeted in each of these areas of research. Enzyme activity has been studied for many decades and many paradigms have evolved but, very recently, tools have been developed that allow the testing of those paradigms with unprecedented levels of detail. We are now able to observe the structure, electronics and dynamics within enzymes at the level of individual atoms. A proper understanding of all of these elements and their interplay is crucial to manipulating enzyme activity, and with observation powers at this level of detail, many of traditional paradigms of enzymology are not surviving rigorous testing. In this study we will examine how enzymes handle chemistry between two entities with the same charge, how the enzyme is triggered to open and close, and how it avoids getting stuck in deep thermodynamic wells when dealing with high-energy reactions. These issues are fundamental to the activity of many enzymes and are not well understood. To achieve the study we will investigate the behaviour of an enzyme that moves phosphate groups between a carboxylate group and a phosphate group, and between two phosphate groups. Enzymes that move phosphate groups lie at the heart of every system in living organisms - in the storage, maintenance and expression of genetic information, in metabolism, communication, cell architecture, differentiation, and homeostasis. We will develop new models based on the behaviour an archetypal enzyme that delivers very high quality measurements, which can then be translated to other enzymes that are common targets in therapeutic, industrial biotechnology and synthetic biology programmes.