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 angstrom resolution. In this adduct, the Pt-II center, upon release of one ammonia ligand, selectively coordinates to the imidazole of His 15. 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.

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

MARZO, TIZIANO;GABBIANI, CHIARA;
2013-01-01

Abstract

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 angstrom resolution. In this adduct, the Pt-II center, upon release of one ammonia ligand, selectively coordinates to the imidazole of His 15. 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.
2013
Messori, L.; Marzo, Tiziano; Gabbiani, Chiara; Valdes, A. A.; Quiroga, A. G.; Merlino, A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/463269
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