Blue Copper Proteins: A rigid machine for efficient electron transfer, a flexible device for metal uptake

Blue Copper Proteins (BCPs) are small and generally soluble copper-containing proteins which participate in monoelectron transfer processes in biological systems. An overview of their electronic and tertiary structure is detailed here. The well-established entatic/rack-induced mechanism is explained by comparing thermodynamic parameters between the folded (tense) and the unfolded (relaxed) forms of the BCP rusticyanin. Recently, NMR solution data have shown that the active sites of BCPs in absence of the metal ion, i.e. in the apoforms, are flexible in the micro-to-second timescale. The rigidity proposed by the entatic/rack-induced mechanism is an imperative for the holoprotein to perform electron transfer; while the flexibility of the apocupredoxin is necessary to uptake the metal ion from the metallochaperones. These apparently contradictory requirements are discussed in the present work. Finally, the role of azurin and some peptides derived from it in anticancer therapy are also described. [Display omitted] •β-barrel in cupredoxins determines the geometry and the electronic structure of the copper ion.•Holocupredoxins fulfill the entatic/rack-induced mechanism, while apoforms are relaxed.•Azurin and rusticyanin can be efficient in anticancer and antimalarial therapies.