title: The unusual binding mechanism of Cu(II) ions to the poly-histidyl domain of a peptide found in the venom of an African viper.
abstract: Copper complexes of a poly-His/poly-Gly peptide (EDDHHHHHHHHHGVGGGGGGGGGG-NH2), a natural component of a snake venom, were studied by means of both experimental (thermodynamic, spectroscopic and MS) techniques and molecular dynamics (MD) simulations and density functional theory (DFT) calculations. This peptide proved to be an exceptionally effective copper chelator, forming complexes which are thermodynamically more stable than those formed by both the albumin-like ATCUN motif and several other poly-histidine protein fragments. We show that, in a poly-histidine stretch, copper seems to prefer binding to residues separated by one amino acid and that a correlation between an α-helical structure of the predicted complexes and their thermodynamic stability is observed.
authors.affiliation: Department of Chemical and Pharmaceutical Sciences, University of Ferrara, via Fossato di Mortara 17, I-44121 Ferrara, Italy. rmm@unife.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pontecchiani
authors.forename: Eyal
authors.initials: E
authors.lastname: Simonovsky
authors.forename: Robert
authors.initials: R
authors.lastname: Wieczorek
authors.forename: Nuno
authors.initials: N
authors.lastname: Barbosa
authors.forename: Magdalena
authors.initials: M
authors.lastname: Rowinska-Zyrek
authors.forename: Slawomir
authors.initials: S
authors.lastname: Potocki
authors.forename: Maurizio
authors.initials: M
authors.lastname: Remelli
authors.forename: Yifat
authors.initials: Y
authors.lastname: Miller
authors.forename: Henryk
authors.initials: H
authors.lastname: Kozlowski
mesh_terms: D000818:Animals; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014757:Viper Venoms / Q000737:chemistry*; D017819:Viperidae
chemical_list: D056831:Coordination Complexes; D010455:Peptides; D014757:Viper Venoms; D006639:Histidine; D003300:Copper