title: Protein Recognition of Gold-Based Drugs: 3D Structure of the Complex Formed When Lysozyme Reacts with Aubipy(c.).
abstract: The structure of the adduct formed in the reaction between Aubipy(c), a cytotoxic organogold(III) compound, and the model protein hen egg white lysozyme (HEWL) has been solved by X-ray crystallography. It emerges that Aubipy(c), after interaction with HEWL, undergoes reduction of the gold(III) center followed by detaching of the cyclometalated ligand; the resulting naked gold(I) ion is found bound to the protein at Gln121. A direct comparison between the present structure and those previously solved for the lysozyme adducts with other gold(III) compounds demonstrates that coordinated ligands play a key role in the protein-metallodrug recognition process. Structural data support the view that gold(III)-based antitumor prodrugs are activated through metal reduction.
authors.affiliation: Department of Chemistry, University of Florence , Via della Lastruccia, 3-13, Florence I-50059, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari , Via Vienna 2, Sassari I-07100, Italy.
authors.forename: Maria Agostina
authors.initials: MA
authors.lastname: Cinellu
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II , via Cintia, Napoli I-80126, Italy ; CNR Institute of Biostructure and Bioimages , via Mezzocannone 16, Napoli I-80100, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Merlino
keywords: Gold-based drugs; metallodrugs; protein−ligand interactions