title: XAS Investigation of Silver(I) Coordination in Copper(I) Biological Binding Sites.
abstract: Silver(I) is an unphysiological ion that, as the physiological copper(I) ion, shows high binding affinity for thiolate ligands; its toxicity has been proposed to be due to its capability to replace Cu(I) in the thiolate binding sites of proteins involved in copper homeostasis. Nevertheless, the nature of the Ag(I)-thiolate complexes formed within cells is poorly understood, and the details of Ag(I) coordination in such complexes in physiologically relevant conditions are mostly unknown. By making use of X-ray absorption spectroscopy (XAS), we characterized the Ag(I) binding sites in proteins related to copper homeostasis, such as the chaperone Atox1 and metallothioneins (MTs), as well as in bioinspired thiolate Cu(I) chelators mimicking these proteins, in solution and at physiological pH. Different Ag(I) coordination environments were revealed: the Ag-S bond length was found to correlate to the Ag(I) coordination number, with characteristic values of 2.40 and 2.49 Å in AgS2 and AgS3 sites, respectively, comparable to the values reported for crystalline Ag(I)-thiolate compounds. The bioinspired Cu(I) chelator L(1) is proven to promote the unusual trigonal AgS3 coordination and, therefore, can serve as a reference compound for this environment. In the Cu(I)-chaperone Atox1, Ag(I) binds in digonal coordination to the two Cys residues of the Cu(I) binding loop, with the AgS2 characteristic bond length of 2.40 ± 0.01 Å. In the multinuclear Ag(I) clusters of rabbit and yeast metallothionein, the average Ag-S bond lengths are 2.48 ± 0.01 Å and 2.47 ± 0.01 Å, respectively, both indicative of the predominance of trigonal AgS3 sites. This work lends insight into the coordination chemistry of silver in its most probable intracellular targets and might help in elucidating the mechanistic aspects of Ag(I) toxicity.
authors.affiliation: CNRS, UMR 5249, CNRS-CEA-UJF; CEA; and University Grenoble Alpes, Laboratoire de Chimie et Biologie des Métaux (LCBM) , F-38054 Grenoble, France.|ESRF, European Synchrotron Radiation Facility , 71 Avenue des Martyrs, 38043 Grenoble, France.
authors.forename: Giulia
authors.initials: G
authors.lastname: Veronesi
authors.affiliation: CNRS, UMR 5249, CNRS-CEA-UJF; CEA; and University Grenoble Alpes, Laboratoire de Chimie et Biologie des Métaux (LCBM) , F-38054 Grenoble, France.|University Grenoble Alpes and CEA, INAC-SCIB , F-38000 Grenoble, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gallon
authors.affiliation: CNRS, UMR 5249, CNRS-CEA-UJF; CEA; and University Grenoble Alpes, Laboratoire de Chimie et Biologie des Métaux (LCBM) , F-38054 Grenoble, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Deniaud
authors.affiliation: University Grenoble Alpes and CEA, INAC-SCIB , F-38000 Grenoble, France.
authors.forename: Bastien
authors.initials: B
authors.lastname: Boff
authors.affiliation: University Grenoble Alpes and CEA, INAC-SCIB , F-38000 Grenoble, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Gateau
authors.affiliation: University Grenoble Alpes and CEA, INAC-SCIB , F-38000 Grenoble, France.
authors.forename: Colette
authors.initials: C
authors.lastname: Lebrun
authors.affiliation: CEA/DSV/iBEB/SBTN , BP 17171, 30207 Bagnols sur Cèze, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Vidaud
authors.affiliation: CEA/DSV/iBEB/SBTN , BP 17171, 30207 Bagnols sur Cèze, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Rollin-Genetet
authors.affiliation: University Grenoble Alpes and CEA, INAC-SCIB , F-38000 Grenoble, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Carrière
authors.affiliation: BM30B/FAME beamline, ESRF , F-38043 Grenoble cedex 9, France.|Observatoire des Sciences de l'Univers de Grenoble, UMS 832 CNRS, Université Joseph Fourier , F-38041 Grenoble, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Kieffer
authors.affiliation: CNRS, UMR 5249, CNRS-CEA-UJF; CEA; and University Grenoble Alpes, Laboratoire de Chimie et Biologie des Métaux (LCBM) , F-38054 Grenoble, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mintz
authors.affiliation: University Grenoble Alpes and CEA, INAC-SCIB , F-38000 Grenoble, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Delangle
authors.affiliation: CNRS, UMR 5249, CNRS-CEA-UJF; CEA; and University Grenoble Alpes, Laboratoire de Chimie et Biologie des Métaux (LCBM) , F-38054 Grenoble, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Michaud-Soret
mesh_terms: D001665:Binding Sites; D003300:Copper / Q000737:chemistry*; D012834:Silver / Q000737:chemistry*; D056928:X-Ray Absorption Spectroscopy / Q000379:methods*
chemical_list: D012834:Silver; D003300:Copper