Title
Cisplatin Preferentially Binds to Zinc Finger Proteins Containing C3H1 or C4 Motif
Author
Siming Yuan, Xin Ding, Yang Cui, Kaiju Wei, Yuchuan Zheng, Yangzhong Liu
Year
2016
Journal
European Journal of Inorganic Chemistry
Abstract
Cisplatin is a widely used anticancer drug for the treatment of a variety of human malignancies. It has been reported that cisplatin could react with a variety of zinc finger proteins (ZFPs) and resulted in structural perturbation, followed by malfunction of proteins. However, some other ZFPs were found unreactive to cisplatin. The difference of the reactivity of various ZFPs remains unclear. Here we investigated the reaction of cisplatin with ZFPs containing different zinc binding motifs (C2H2, C3H and C4). The zinc release assay and NMR spectroscopy revealed that both C3H and C4 type of ZFPs are highly reactive to cisplatin, whereas the C2H2 type of ZFP is rather inert. The platination of ZFPs caused the zinc ejection from the protein and disrupted the secondary structure. The time dependent HPLC measurement showed that the reaction of C3H and C4 type of ZFPs were also kinetically more favorable than the C2H2 type of ZFPs. ESI-MS data confirmed the binding of upto three platinum atoms to the C3H and C4 ZFPs, whereas only minor amount of mono-platinated C2H2 ZFP was formed. These results indicate that cisplatin preferentially binds to ZFPs containing C3H or C4 Motifs, which could be correlated to the protein selectivity of cisplatin in the cellular environment.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Ligand binding, Biochemistry