Messori, Luigi and Cinellu, Maria Agostina and Merlino, Antonello (2014) Protein recognition of gold-based drugs: 3D structure of the complex formed when lysozyme reacts with Aubipyc. ACS Medicinal Chemistry Letters, Vol. 5 (10), p. 1110-1113. eISSN 1948-5875. Article.
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The structure of the adduct formed in the reaction between Aubipyc, a cytotoxic organogold(III) compound, and the model protein hen egg white lysozyme (HEWL) has been solved by X-ray crystallography. It emerges that Aubipyc, 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.
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