title: Copper(II) interaction with the Human Prion 103-112 fragment - Coordination and oxidation.
abstract: The prion protein (PrP) is a membrane-anchored cell surface glycoprotein containing 231 amino acids. It has been associated with a group of neurodegenerative disorders. Copper(II) interaction with the Human Prion 103-112 fragment and its mutants has been studied with various techniques. The studied human prion fragment contains both histidine and methionine residues, while methionine residues are systematically replaced or displaced in the studied mutants. pH-potentiometric, UV-Vis and circular dicroism spectroscopic techniques were applied to study the stoichiometry, stability and structure of the copper(II) complexes, while HPLC-MS and MS/MS were used for identifying the products of copper(II) catalyzed oxidation. The complex formation reactions of the studied ligands are rather similar; only 1:1 complexes are formed, where the imidazole nitrogen of the histidine residue is the main binding site beside the amide nitrogens of the peptide chain. The only difference is, that in the peptides which contain methionine in position 109, in addition to the (Nim,N-,N-) coordination mode, a weak interaction of thioether sulfur atoms can be supposed. The mutant peptide which does not contain methionine did not undergo oxidation, only the fragmentation of the peptide chain was perceived. However, in the case of methionine containing peptides, the peptide chain was not cleaved; but the oxidation of methionine to methionine sulfoxide occurred.
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Debrecen, H-4032 Debrecen, Hungary.
authors.forename: Gizella
authors.initials: G
authors.lastname: Csire
authors.affiliation: Department of Applied Chemistry, University of Debrecen, H-4032 Debrecen, Hungary.
authors.forename: Lajos
authors.initials: L
authors.lastname: Nagy
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Debrecen, H-4032 Debrecen, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Várnagy
authors.affiliation: MTA-DE Homogeneous Catalysis and Reaction Mechanisms Research Group, University of Debrecen, H-4032 Debrecen, Hungary. Electronic address: kallay.csilla@science.unideb.hu.
authors.forename: Csilla
authors.initials: C
authors.lastname: Kállay
mesh_terms: D019943:Amino Acid Substitution; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008715:Methionine / Q000737:chemistry / Q000235:genetics; D020125:Mutation, Missense; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D000072002:Prion Proteins / Q000737:chemistry* / Q000235:genetics; D055550:Protein Stability
chemical_list: D010455:Peptides; D000072002:Prion Proteins; D003300:Copper; D008715:Methionine