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

Identifieur interne : 000120 ( Main/Exploration ); précédent : 000119; suivant : 000121

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

Auteurs : Irene Russo Krauss [Italie] ; Giarita Ferraro [Italie] ; Antonello Merlino [Italie]

Source :

RBID : pubmed:27482735

Descripteurs français

English descriptors

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.

DOI: 10.1021/acs.inorgchem.6b01234
PubMed: 27482735


Affiliations:


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Le document en format XML

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<term>Binding Sites (MeSH)</term>
<term>Cisplatin (chemistry)</term>
<term>Cisplatin (metabolism)</term>
<term>Crystallography, X-Ray (MeSH)</term>
<term>Hydrolysis (MeSH)</term>
<term>Lysine (metabolism)</term>
<term>Plant Proteins (chemistry)</term>
<term>Plant Proteins (metabolism)</term>
<term>Protein Conformation (MeSH)</term>
<term>Spectrophotometry, Ultraviolet (MeSH)</term>
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<term>Cisplatine (composition chimique)</term>
<term>Cisplatine (métabolisme)</term>
<term>Conformation des protéines (MeSH)</term>
<term>Cristallographie aux rayons X (MeSH)</term>
<term>Hydrolyse (MeSH)</term>
<term>Lysine (métabolisme)</term>
<term>Protéines végétales (composition chimique)</term>
<term>Protéines végétales (métabolisme)</term>
<term>Sites de fixation (MeSH)</term>
<term>Spectrophotométrie UV (MeSH)</term>
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<term>Plant Proteins</term>
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<term>Plant Proteins</term>
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<term>Protéines végétales</term>
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<term>Cristallographie aux rayons X</term>
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<div type="abstract" xml:lang="en">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. </div>
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