Peculiar features in the crystal structure of the adduct formed between cis-PtI2(NH3)2 and hen egg white lysozyme.

The reactivity of cis-diamminediiodidoplatinum(II), cis-PtI2(NH3)2, the iodo analogue of cisplatin, with hen egg white lysozyme (HEWL) was investigated by electrospray ionization mass spectrometry and X-ray crystallography. Interestingly, the study compound forms a stable 1:1 protein adduct for which the crystal structure was solved at 1.99 Å resolution. In this adduct, the Pt(II) center, upon release of one ammonia ligand, selectively coordinates to the imidazole of His15. Both iodide ligands remain bound to platinum, with this being a highly peculiar and unexpected feature. Notably, two equivalent modes of Pt(II) binding are possible that differ only in the location of I atoms with respect to ND1 of His15. The structure of the adduct was compared with that of HEWL-cisplatin, previously described; differences are stressed and their important mechanistic implications discussed.

[1]  A. Trapananti,et al.  Interaction of cisplatin with human superoxide dismutase. , 2012, Journal of the American Chemical Society.

[2]  A. Timerbaev,et al.  Recent progress in the application of analytical techniques to anticancer metallodrug proteomics , 2011 .

[3]  Jan Reedijk,et al.  New clues for platinum antitumor chemistry: Kinetically controlled metal binding to DNA , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[4]  A. Carnero,et al.  The second generation of iodido complexes: trans-[PtI2(amine)(amine')] bearing different aliphatic amines. , 2013, Journal of inorganic biochemistry.

[5]  A. Casini,et al.  Reactivity of an antimetastatic organometallic ruthenium compound with metallothionein-2: relevance to the mechanism of action. , 2009, Metallomics : integrated biometal science.

[6]  Dong Wang,et al.  Cellular processing of platinum anticancer drugs , 2005, Nature Reviews Drug Discovery.

[7]  M. Palacios,et al.  SEC-ICP-MS and ESI-MS as tools to study the interaction between cisplatin and cytosolic biomolecules , 2007 .

[8]  C. Supuran,et al.  ESI mass spectrometry and X-ray diffraction studies of adducts between anticancer platinum drugs and hen egg white lysozyme. , 2007, Chemical communications.

[9]  A. Casini,et al.  Mass spectrometric analysis of ubiquitin–platinum interactions of leading anticancer drugs: MALDI versus ESI , 2007 .

[10]  R. Mandal,et al.  Mass spectrometric studies of cisplatin-induced changes of hemoglobin. , 2003, Rapid communications in mass spectrometry : RCM.

[11]  A. Casini,et al.  Biophysical characterisation of adducts formed between anticancer metallodrugs and selected proteins: new insights from X-ray diffraction and mass spectrometry studies. , 2008, Journal of inorganic biochemistry.

[12]  C. Costello,et al.  A Mass Spectral Study of the Binding of the Anticancer Drug Cisplatin to Ubiquitin , 1999 .

[13]  A. Casini,et al.  Structural investigation of cisplatin-protein interactions: selective platination of His19 in a cuprozinc superoxide dismutase. , 2006, Angewandte Chemie.

[14]  I. Bertini,et al.  Probing the interaction of cisplatin with the human copper chaperone Atox1 by solution and in-cell NMR spectroscopy. , 2011, Journal of the American Chemical Society.

[15]  Fuyi Wang,et al.  A comparative study on interactions of cisplatin and ruthenium arene anticancer complexes with metallothionein using MALDI-TOF-MS , 2011 .

[16]  P. Cramer,et al.  Mechanism of transcriptional stalling at cisplatin-damaged DNA , 2007, Nature Structural &Molecular Biology.

[17]  V. Brabec.  DNA modifications by antitumor platinum and ruthenium compounds: their recognition and repair. , 2002, Progress in nucleic acid research and molecular biology.

[18]  J. Hoeschele,et al.  Studies on the antitumor activity of group VIII transition metal complexes. Part I. Platinum (II) complexes , 1973 .

[19]  F. L. King,et al.  Direct determination of the primary binding site of cisplatin on cytochrome c by mass spectrometry , 2009, Journal of the American Society for Mass Spectrometry.

[20]  W. Sheldrick,et al.  Interaction of cisplatin with methionine- and histidine-containing peptides: competition between backbone binding, macrochelation and peptide cleavage , 2001, JBIC Journal of Biological Inorganic Chemistry.

[21]  C. S. Allardyce,et al.  Determination of drug binding sites to proteins by electrospray ionisation mass spectrometry: the interaction of cisplatin with transferrin. , 2002, Rapid communications in mass spectrometry : RCM.

[22]  A. Casini,et al.  Exploring Metallodrug–Protein Interactions by ESI Mass Spectrometry: The Reaction of Anticancer Platinum Drugs with Horse Heart Cytochrome c , 2006, ChemMedChem.

[23]  A. Rosenzweig,et al.  Crystal structures of cisplatin bound to a human copper chaperone. , 2009, Journal of the American Chemical Society.

[24]  A. Casini,et al.  Reactivity and biological properties of a series of cytotoxic PtI2(amine)2 complexes, either cis or trans configured. , 2012, Inorganic chemistry.