The Reaction of Arsenite with Proteins Relies on Solution Conditions

详细信息    查看全文

• 作者：Linhong Zhao ; Zhen Wang ; Zhaoyong Xi ; Dechen Xu ; Siming Chen ; Yangzhong Liu
• 刊名：Inorganic Chemistry
• 出版年：2014
• 出版时间：March 17, 2014
• 年：2014
• 卷：53
• 期：6
• 页码：3054-3061
• 全文大小：326K
• 年卷期：v.53,no.6(March 17, 2014)
• ISSN：1520-510X

文摘

Arsenic is a biologically interesting element with both antitumor and carcinogenic effects. Zinc finger proteins (ZFPs) have been confirmed to be the cellular targets of arsenite; however, arsenite inhibits ZFPs much less efficiently in vitro than in vivo. The molecular mechanism of this difference is unknown. In this work, we found that the reaction of arsenite with ZFPs relies on the presence of small biomolecules such as glutathione (GSH), histidine, and cysteine (Cys). The weak acidity also enhances the reaction. Further study shows that the coordination of zinc is much more susceptible than that of arsenic to these solution conditions, which enhance the competition of arsenic. Notably, different from C₃H-type ZFPs, the C₂H₂-type ZFPs are more significantly influenced by the presence of thiol-containing molecules in the reaction. GSH and Cys can facilitate the reaction by participation of the coordination to As(III) together with C₂H₂-type ZFPs. Consequently, the reactions are promoted both thermodynamically and kinetically via the formation of ternary complexes GSH-As-ZFP or Cys-As-ZFP. These results indicate that the reactions between arsenite and proteins are considerably modulated by environments such as the small biomolecules and the acidity of the solution. This finding clarifies the discrepancy observed in the reactions of arsenite in vitro versus in cells, and provides an insight into the molecular mechanism of arsenite.