title: Mixed metal copper(II)-nickel(II) and copper(II)-zinc(II) complexes of multihistidine peptide fragments of human prion protein.
abstract: Mixed metal copper(II)-nickel(II) and copper(II)-zinc(II) complexes of four peptide fragments of human prion protein have been studied by potentiometric, UV-vis and circular dichroism spectroscopic techniques. One peptide contained three histidyl residues: HuPrP(84-114) with H85 inside and H96, H111 outside the octarepeat domain. The other three peptides contained two histidyl residues; H96 and H111 for HuPrP(91-115) and HuPrP(84-114)H85A while HuPrP(84-114)H96A contained the histidyl residues at positions 85 and 111. It was found that both histidines of the latter peptides can simultaneously bind copper(II) and nickel(II) ions and dinuclear mixed metal complexes can exist in slightly alkaline solution. One molecule of the peptide with three histidyl residues can bind two copper(II) and one nickel(II) ions. H85 and H111 were identified as the major copper(II) and H96 as the preferred nickel(II) binding sites in mixed metal species. The studies on the zinc(II)-PrP peptide binary systems revealed that zinc(II) ions can coordinate to the 31-mer PrP peptide fragments in the form of macrochelates with two or three coordinated imidazol-nitrogens but the low stability of these complexes cannot prevent the hydrolysis of the metal ion in slightly alkaline solution. These data provide further support for the outstanding affinity of copper(II) ions towards the peptide fragments of prion protein but the binding of nickel(II) can significantly modify the distribution of copper(II) among the available metal binding sites.
authors.affiliation: University of Debrecen, Department of Inorganic and Analytical Chemistry, H-4010 Debrecen, Hungary.
authors.forename: Viktória
authors.initials: V
authors.lastname: Jószai
authors.forename: Ildikó
authors.initials: I
authors.lastname: Turi
authors.forename: Csilla
authors.initials: C
authors.lastname: Kállay
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pappalardo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Natale
authors.forename: Enrico
authors.initials: E
authors.lastname: Rizzarelli
authors.forename: Imre
authors.initials: I
authors.lastname: Sóvágó
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002712:Chlorides / Q000737:chemistry*; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D006639:Histidine / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D009532:Nickel / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000737:chemistry; D011328:Prions / Q000737:chemistry*; D011498:Protein Precursors / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D017967:Zinc Compounds / Q000737:chemistry*
chemical_list: D002712:Chlorides; D056831:Coordination Complexes; C108999:PACAP-related peptide; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011328:Prions; D011498:Protein Precursors; D017967:Zinc Compounds; D006639:Histidine; C022838:nickel chloride; D003300:Copper; D009532:Nickel; C016837:zinc chloride; C029892:cupric chloride