Abstract
For many decades, it has been widely accepted that copper is an essential trace element required for survival by all organisms from bacterial cells to humans (1). What is so special about this trace element that makes it essential in biology? Copper ions undergo unique chemistry because of their ability to adopt distinct redox states, either oxidized, Cu(II), or reduced, Cu(I). Consequently, Cu ions serve as important catalytic cofactors in redox chemistry for proteins that carry out fundamental biological functions required for growth and development (Table 1). Copper proteins show a variety of functions (Table 2) and can be classified by the kind and number of prosthetic centers (Table 3) and/or by the Cu center type found in the protein structure (Table 4). Copper-requiring proteins are involved in a variety of biological processes, and metal deficiency in these enzymes, or alteration in its activity, often causes disease states or pathophysiological conditions. Although it is clear that Cu is essential, it is also a potent cytotoxic agent when allowed to accumulate in excess with respect to cellular needs. In fact, because of its special redox chemistry, copper readily participates in reactions that result in the production of highly reactive oxygen species (ROS), including hydroxyl radicals (2). Hydroxyl radicals are believed to be responsible for devastating cellular damage that includes lipid peroxidation in membranes, direct oxidation of proteins, and cleavage of DNA and RNA molecules. Indeed, the generation and action of ROS are thought to be major contributing factors to the development of cancer, disease of the nervous system, and aging (3). In addition to the generation of ROS, Cu may manifest its toxicity by displacing other metals cofactors from their natural ligands in key cellular signaling proteins. It is highly likely that Cu is able to displace metal ions in a number of catalytic or structural motifs in many cellular proteins. Given that Cu is both essential and toxic, organisms must implement uptake mechanisms to extract Cu from nutrients, transport Cu across the biological membranes, and deliver it to Cu-requiring proteins. Furthermore, precise regulatory mechanisms must be in place to prevent the accumulation of Cu ions to toxic levels (4). Details of the structure and dynamics behavior of copper proteins at atomic resolution are central to understanding mechanism of catalysis, ligand binding, allosteric modulation, and protein—protein interaction.
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Falconi, M., Desideri, A. (2002). Molecular Modeling and Dynamics of Copper Proteins. In: Massaro, E.J. (eds) Handbook of Copper Pharmacology and Toxicology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-288-3_4
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