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The ability of copper to cycle its oxidation state, and to form high-affinity complexes with a range of biologically relevant ligands, underpins the central role that this metal plays in prokaryotic processes such as respiration, oxidative stress response, the nitrogen cycle and pigmentation. However, the very properties that nature has exploited also mean that copper is extremely toxic. To minimize this toxicity, while also ensuring sufficient supply of the metal, complex systems of trafficking evolved to facilitate transport of copper (as Cu(I)) across membranes and its targeted distribution within the cytoplasm, membrane and periplasm. The past 20 years have seen our understanding of such systems grow enormously, and atomic/molecular and mechanistic detail of many of the major cellular trafficking components is now available. This chapter begins with a discussion of the chemistry of copper that is relevant for understanding the role of this metal throughout life. The subsequent focus is then on current understanding of copper homeostasis in prokaryotes, with eukaryotic copper homeostasis dealt with in the following chapters. The chapter aims to provide a chemical perspective on these complex biological systems, emphasizing the importance of thermodynamic and kinetic properties of copper and the complexes it forms.

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