title: Cisplatin-Protein Interactions: Unexpected Drug Binding to N-Terminal Amine and Lysine Side Chains.
abstract: Literature studies carried out by mass spectrometry and X-ray crystallography have demonstrated that cisplatin is able to bind proteins mainly close to Met, His, and free Cys side chains. To identify possible alternative modes of cisplatin binding to proteins at the molecular level, here we have solved the high-resolution X-ray structure of the adduct formed in the reaction between the drug and the model protein thaumatin, which does not contain any His and free Cys residues and possesses just one buried Met. Our data reveal unexpected cisplatin binding sites on the protein surface that could have general significance: cisplatin fragments -[Pt(NH3)2Cl](+), -[Pt(NH3)Cl2], and -[Pt(NH3)2(OH2)](2+) bind to a protein N-terminus and close to Lys and Glu side chains.
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II , Via Cintia, I-80126 Naples, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Russo Krauss
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II , Via Cintia, I-80126 Naples, Italy.
authors.forename: Giarita
authors.initials: G
authors.lastname: Ferraro
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II , Via Cintia, I-80126 Naples, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Merlino
mesh_terms: D001665:Binding Sites; D002945:Cisplatin / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D006868:Hydrolysis; D008239:Lysine / Q000378:metabolism*; D010940:Plant Proteins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D013056:Spectrophotometry, Ultraviolet
chemical_list: D010940:Plant Proteins; C003427:thaumatin protein, plant; D008239:Lysine; D002945:Cisplatin