Cu-coordination changes triggered by external ligands

In order to control their high redox activity, in living systems Cu ions are normally coordinated to proteins and short peptides. One of the main functions of Cu in biology is as a catalytic redox centre in enzymes where the role of Cu is often to activate dioxygen. The coordination chemistry of Cu(II) and Cu(I) bound to intrinsically disordered proteins (IDPs) are very different (e.g. in the case of amyloid-β peptide related to Alzheimer’s disease). Similar differences in the coordination chemistry is also reported in the Cu-α-synuclein that is related to Parkinson disease. Such flexible Cu-IDP are quite competent in di-oxygen activation to form reactive oxygen species, which could contribute to the oxidative stress observed in the diseases.Hence a central question is how this redox process can occur. In fact, going from Cu(II) to Cu(I) and back needs a quite important rearrangement of the peptide around the Cu-ion. Answering this question is the main goal of the present proposal.