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Interaction of divalent cations with Park9 protein

Zoroddu, Maria Antonietta and Peana, Massimiliano Francesco and Medici, Serenella and Remelli, Maurizio (2012) Interaction of divalent cations with Park9 protein. In: AsBIC VI: the 6. Asian biological inorganic chemistry conference, November 5-8, 2012, Hong-Kong, China. [S.l.], [s.n.]. p. 62. Conference or Workshop Item.

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Abstract

We have tested two peptide sequences from Park9 Parkinson’s disease (PD) gene, -P1D2E3K4H5E6L7- and -F1C2G3D4G5A6N7D8C9G10- (2), 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. 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. To understand the details of their metal binding sites at different pH values and at different ligand to metal molar ratios, mono- and multidimensional NMR spectroscopy, together with potentiometric and UV-vis experiments, have been used, showing that the three metals are able to effectively bind the examined peptides. Mn(II) and Zn(II) coordination with peptide involves imidazol Nε or Nδ of His5 and carboxyl γ-O of Asp2, Glu3 and Glu6 residues. Six donor atoms participate in Mn(II) binding, resulting in a distorted octahedral geometry, possibly involving bidentate interaction of carboxyl groups; four donor atoms participate in Zn(II) binding, resulting in a tetracoordinated geometry. Mn(II) and Zn(II) coordination involves the two cysteine residues with peptide; Mn(II) accepts additional ligand bonds from D4 and D8 to complete the coordination sphere, together with some water molecules.

Item Type:Conference or Workshop Item (Poster)
ID Code:8965
Status:Published
Uncontrolled Keywords:Park9, Parkinson, manganese, copper, zinc
Subjects:Area 03 - Scienze chimiche > CHIM/03 Chimica generale e inorganica
Divisions:001 Università di Sassari > 01 Dipartimenti > Chimica
Publisher:[s.n.]
Deposited On:03 May 2013 08:58

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