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