Title
Effect of platinum anticancer drugs on the cytochrome c conformation
Author
Urszula Śliwińska-Hill, Lilianna Trynda-Lemiesz
Year
2017
Journal
Inorganica Chimica Acta
Abstract
Cytochrome c is an important electron transfer carrier in mitochondrial electron transfer and is essential for apoptosis. In the present work we have examined the effect of platinum (II) complexes (cisplatin, transplatin and carboplatin) on the conformation of cytochrome c and the state of heme moiety. For this purpose, UV–VIS spectroscopy, circular dichroism (CD) and absorption second derivative spectroscopy methods have been used. Moreover, the amount of platinum per mole of cytochrome c and stability of carboplatin–cytochrome c system have been determined by ICP-AES and zeta potential measurements, respectively. The present data has revealed that binding of platinum (II) complexes to cytochrome c induces a conformation of the protein with less organized tertiary structure. Determination of tyrosine exposure by second-derivative spectroscopy indicates changes occurring in the tyrosyl microenvironment, which becomes more polar following the more open conformation compared to that of a native protein. The reaction of cytochrome c with platinum complexes led to the changes in spectral properties, most notably the decreases in intensity of the absorption band at 695 nm, indicating that platinum complexes may affect coordination Met-80 with the heme iron. Under physiological conditions the carboplatin-cytochrome c system shows instability, what is desired effect from the pharmacological point of view.
Instrument
J-715
Keywords
Circular dichroism, Secondary structure, Biochemistry