Inner- and outer-sphere metal coordination in blue copper proteins

Blue copper proteins (BCPs) comprise classic cases of Nature's profound control over the electronic structures and chemical reactivity of transition metal ions. Early studies of BCPs focused on their inner coordination spheres, that is, residues that directly coordinate Cu. Equally important are the electronic and geometric perturbations to these ligands provided by the outer coordination sphere. In this tribute to Hans Freeman, we review investigations that have advanced the understanding of how inner-sphere and outer-sphere coordination affects biological Cu properties.

Graphical abstractIn this tribute to Hans Freeman, we review investigations of how inner-sphere and outer-sphere coordination affects blue Cu properties, such as in Pseudomonas aeruginosa azurin (shown).Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► We present a focused review of metal coordination in blue copper proteins. ► Inner- and outer-sphere interactions tune properties of copper sites. ► Electronic structure and chemical reactivity of blue copper centers are discussed.