Volume:  2 Year:  2012 Symposium Edition:  XXIII ISMEC GROUP SERIES

Two peptide sequences from Park9 Parkinson’s disease (PD) gene,-P1D2E3K4H5E6L7- (1) and-F1C2G3D4G5A6N7D8C9G10- (2) have been tested for Mn(II), Zn(II) and Cu(II) binding. Park9 encoded protein can protect cells from manganese poisoning, which is an environmental risk factor for a Parkinson’s disease-like syndrome [1-4]. In fact, Park9 belongs to a family of ATP-ases involved in metal coordination and transportation; familial gene mutations may result in early development of PD. The chosen fragments are located from 1165 to 1171 and from 1184 to 1193 residues in the Park9 sequence, and are highly conserved in a number of organisms, going from yeasts to humans. Potentiometric, UV-vis experiments together with mono- and multidimensional NMR spectroscopy have been used to understand the details of metal binding sites at different pH values and at different ligand to metal molar ratios, showing that the three metals are able to effectively bind the examined peptides. From NMR measurements Mn(II) and Zn(II) coordination with peptide 1 involves imidazole Nε or Nδ of His5 and carboxyl γ-O of Asp2, Glu3 and Glu6 residues