A theoretical study on Cu(II) binding modes and antioxidant activity of mammalian normal prion protein

In this paper, the density functional theory (DFT) method B3LYP/LANL2DZ was used to calculate binding energies and electron affinities for various Cu(II) binding modes of mammalian normal prion protein (PrPc). The calculation results not only provide solid evidence to support one of the experimentally determined Cu(II) binding modes of PrPc but also shed new light on the normal function of the elusive protein; that is, PrPc is rather a Cu(II) transporter than an antioxidant. In addition, the employed theoretical methodology is also useful to investigate the metal chelating properties of other proteins and to rationally design Cu,Zn-superoxide dismutase mimics.