Dynamics of Electron and Proton Transfer Chemistry in Copper and Hybrid Copper-Haem Enzymes

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The mechanisms of effective electron and proton transfer in chemical processes, to catalyse chemical reactions and enable essential biochemical functions, are still not fully understood. This proposal combines state of the art experimental and high performance computational methods to address these questions, developing innovative approaches with a focus on proteins that perform fundamental chemistry that is important to the environment as part of the global nitrogen cycle. New experimental methods include rapid room temperature X-ray crystallography and single crystal spectroscopies, while the theoretical approach will be a mixture of quantum mechanics, molecular mechanics and molecular dynamics, with the calculations performed on state of the art parallel processing computer systems.Copper nitrite reductases are important environmental proteins that carry out the chemistry to convert nitrite (NO2) to nitric oxide (NO) during the process of denitrification, a key step of the biological 'nitrogen cycle' whereby nitrogen gas is returned from the soil to the atmosphere. We will first study this process in an enzyme from Achromobacter cycloclastes. It requires binding of NO2 to a Cu atom and its reduction to NO via mechanisms involving a second Cu atom and electron and proton transfer to the 'active site'. This also normally involves the formation of a normally transient complex between the nitrite reductase and a cytochrome (electron donor) partner protein, making the chemistry difficult to study. Recently a new nitrite reductase has been discovered that contains a 'tethered' cytochrome domain. This protein, from Ralstonia picketti, acts as a 'self-contained electron transfer' system, an unusual and rare structure that negates the need for a transient protein-protein complex and which provides us with the unique opportunity to fully study such a fundamental catalytic process in detail, ie electron transfer, proton transfer, NO2 delivery and binding, as well as the metal oxidation states.The outcomes of our programme will be of broad relevance to any chemistry involving controlled electron and proton transfer reactions, processes that are ubiquitous in nature, and essential for future development of efficient biomimetic compounds or synthetic enzymes & enzyme-inspired catalysts for industrial applications.