Critical target identification and human health risk ranking of metal ions based on mechanism-driven modeling

doi:10.1016/j.chemosphere.2022.134724

	Critical target identification and human health risk ranking of metal ions based on mechanism-driven modeling
	Wang, Xiaoqing1,3 ; Teng, Yuefa 1,3; Ji, Chenglong1,2,4 ; Wu, Huifeng1,2,4 ; Li, Fei1,4
发表期刊	CHEMOSPHERE
ISSN	0045-6535
	2022-08-01
卷号	301 页码:9
关键词	Metal ions p53 QSAR Genetic toxicity Human health risk
DOI	10.1016/j.chemosphere.2022.134724
英文摘要	Huge amounts of metals have been released into environment due to various anthropogenic activities, such as smelting and processing of metals and subsequent application in construction, automobiles, batteries, optoelectronic devices, and so on, resulting in widespread detection in environmental media. However, some metal ions are considered as "Environmental health hazards", leading to serious human health concerns through affecting critical targets. Hence, it is necessary to quickly and effectively recognize the key target of metal ions in living organisms. Fortunately, the development of high-throughput analysis and in silico approaches offer a promising tool for target identification. In this study, the key oncogenic target (tumor suppressor protein, p53) was screened by network analysis based on the comparative toxicogenomics database (CTD). Some metal ions could bind to p53 core domain, impair its function and induce the development of cancer risk, but its mechanisms were still unclear. Therefore, a quantitative structure-activity relationship (QSAR) model was constructed to characterize the binding constants (K-a) between DNA binding domain of p53 (p53 DBD) and nine metal ions (Mg2+, Ca2+, Cu2+, Zn2+, Co2+, Ni2+, Mn2+, Fe3+ and Ba2+). It had good robustness and predictive ability, which could be used to predict the Ka values of other six metal ions (Li+, Ag+, Cs+, Cd2+, Hg2+ and Pb2+) within application domain. The results showed strong binding affinity between Cd2+/Hg2+/Pb2+ and p53 DBD. Subsequent mechanism analyses revealed that first hydrolysis constant (vertical bar logK(OH)vertical bar) and polarization force (Z(2)/r) were key metal ion-characteristic parameters. The metal ions with weak hydrolysis constants and strong polarization forces could readily interact with N-containing histidine and S-containing cysteine of p53 DBD, which resulted in high K-a values. This study identified p53 as potential target for metal ions, revealed the key characteristics affecting the actions and provide a basic understanding of metal ions-p53 DBD interaction.
收录类别	SCI
语种	英语
关键词[WOS]	RELATIVE TOXICITY ; IN-VITRO ; CANCER CELLS ; DNA-BINDING ; P53 ; PREDICTION ; QSAR ; DOCKING ; DOMAIN ; WATER
研究领域[WOS]	Environmental Sciences & Ecology
WOS记录号	WOS:000799858700004
引用统计	被引频次：3[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.yic.ac.cn/handle/133337/31163
专题	中国科学院海岸带环境过程与生态修复重点实验室中国科学院海岸带环境过程与生态修复重点实验室_海岸带环境过程实验室
通讯作者	Wu, Huifeng; Li, Fei
作者单位	1.Chinese Acad Sci, Yantai Inst Coastal Zone Res YIC, CAS Key Lab Coastal Environm Proc & Ecol Remediat, Shandong Key Lab Coastal Environm Proc,YICCAS, Yantai 264003, Peoples R China 2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Fisheries Sci & Food Prod Proc, Qingdao 266237, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Ctr Ocean Mega Sci, Qingdao 266071, Peoples R China
推荐引用方式 GB/T 7714	Wang, Xiaoqing,Teng, Yuefa,Ji, Chenglong,et al. Critical target identification and human health risk ranking of metal ions based on mechanism-driven modeling[J]. CHEMOSPHERE,2022,301:9.
APA	Wang, Xiaoqing,Teng, Yuefa,Ji, Chenglong,Wu, Huifeng,&Li, Fei.(2022).Critical target identification and human health risk ranking of metal ions based on mechanism-driven modeling.CHEMOSPHERE,301,9.
MLA	Wang, Xiaoqing,et al."Critical target identification and human health risk ranking of metal ions based on mechanism-driven modeling".CHEMOSPHERE 301(2022):9.