title: Cadmium-glutathione solution structures provide new insights into heavy metal detoxification.
abstract: Cadmium is a heavy metal and a pollutant that can be found in large quantities in the environment from industrial waste. Its toxicity for living organisms could arise from its ability to alter thiol-containing cellular components. Glutathione is an abundant tripeptide (γ-Glu-Cys-Gly) that is described as the first line of defence against cadmium in many cell types. NMR experiments for structure and dynamics determination, molecular simulations, competition reactions for metal chelation by different metabolites (γ-Glu-Cys-Gly, α-Glu-Cys-Gly and γ-Glu-Cys) combined with biochemical and genetics experiments have been performed to propose a full description of bio-inorganic reactions occurring in the early steps of cadmium detoxification processes. Our results give unambiguous information about the spontaneous formation, under physiological conditions, of the Cd(GS)(2) complex, about the nature of ligands involved in cadmium chelation by glutathione, and provide insights on the structures of Cd(GS)(2) complexes in solution at different pH. We also show that γ-Glu-Cys, the precursor of glutathione, forms a stable complex with cadmium, but biological studies of the first steps of cadmium detoxification reveal that this complex does not seem to be relevant for this purpose.
authors.affiliation: Laboratoire de Biologie Intégrative/Service de Biologie Intégrative et Génétique Moléculaire/Institut de Biologie et de Technologies de Saclay, CEA-Saclay, Gif-sur-Yvette Cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Delalande
authors.forename: Hervé
authors.initials: H
authors.lastname: Desvaux
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Godat
authors.forename: Alain
authors.initials: A
authors.lastname: Valleix
authors.forename: Christophe
authors.initials: C
authors.lastname: Junot
authors.forename: Jean
authors.initials: J
authors.lastname: Labarre
authors.forename: Yves
authors.initials: Y
authors.lastname: Boulard
mesh_terms: D002104:Cadmium / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D019281:Dimerization; D005978:Glutathione / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008658:Inactivation, Metabolic; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012996:Solutions
chemical_list: D012996:Solutions; D002104:Cadmium; D005978:Glutathione