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.

Cisplatin-Protein Interactions: Unexpected Drug Binding to N-Terminal Amine and Lysine Side Chains / RUSSO KRAUSS, Irene; Ferraro, Giarita; Merlino, Antonello. - In: INORGANIC CHEMISTRY. - ISSN 0020-1669. - 55:16(2016), pp. 7814-6-7816. [10.1021/acs.inorgchem.6b01234]

Cisplatin-Protein Interactions: Unexpected Drug Binding to N-Terminal Amine and Lysine Side Chains

RUSSO KRAUSS, IRENE;FERRARO, GIARITA;MERLINO, ANTONELLO
2016

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.
2016
Cisplatin-Protein Interactions: Unexpected Drug Binding to N-Terminal Amine and Lysine Side Chains / RUSSO KRAUSS, Irene; Ferraro, Giarita; Merlino, Antonello. - In: INORGANIC CHEMISTRY. - ISSN 0020-1669. - 55:16(2016), pp. 7814-6-7816. [10.1021/acs.inorgchem.6b01234]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/637643
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