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A Mass Spectrometric and Molecular Modelling Study of Cisplatin Binding to Transferrin
Author(s) -
Khalaila Isam,
Allardyce Claire S.,
Verma Chandra S.,
Dyson Paul J.
Publication year - 2005
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200500067
Subject(s) - cisplatin , chemistry , binding site , transferrin , mass spectrometry , binding protein , plasma protein binding , stereochemistry , biochemistry , biophysics , biology , chromatography , genetics , chemotherapy , gene
A combination of mass spectrometry, UV/Vis spectroscopy and molecular modelling techniques have been used to characterise the interaction of cisplatin with human serum transferrin (Tf). Mass spectrometry indicates that cisplatin binds to the hydroxy functional group of threonine 457, which is located in the iron( III )‐binding site on the C‐terminal lobe of the protein. UV/Vis spectroscopy confirms the stoichiometry of binding and shows that cisplatin and iron( III ) binding are competitive. The binding of cisplatin has been modelled by using molecular dynamic simulations and the results suggest that cisplatin can occupy part of both the iron( III )‐ and carbonate‐binding sites in the C‐terminal lobe of the protein. Combined, the studies suggest that cisplatin binding sterically restricts iron( III ) binding to the C‐terminal lobe binding site, whereas the N‐terminal lobe binding site appears to be unaffected by the cisplatin interaction, possibly allowing the iron( III )‐induced conformational change necessary for binding to a Tf receptor.