Protein-metallodrugs interactions: Effects on the overall protein structure and characterization of Au, Ru and Pt binding sites

The effects of metalation process by inorganic compounds containing Au, Pt and Ru on protein structure and on conformation and flexibility of the residues involved in the metal compound binding have been here investigated by analysing 204 structures of protein/metallodrug adducts and the corresponding metal-free forms. The overall structure of the proteins is not significantly affected by the metal label. 162 non-redundant protein residues involved in Au, Pt and Ru coordination have been identified. In the metal-free protein structures these residues often belong to alpha-helical regions and show low flexibility. They do not necessarily belong to outer layers of the protein structure. In the majority of the adducts, the side chains of these residues adopt a conformation that is similar to that observed in the metal-free protein. The metal coordination reduces their solvent accessible surface area without altering their overall flexibility. These results could be useful for the prediction of residues able to bind Au, Pt and Ru compounds. (C) 2020 Elsevier B.V. All rights reserved.