Critical target identification and human health risk ranking of metal ions based on mechanism-driven modeling
文献类型：期刊论文
| 作者 | Wang, Xiaoqing2,4 ; Teng, Yuefa2,4; Ji, Chenglong1,3,4; Wu, Huifeng1,3,4; Li, Fei1,4
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| 刊名 | CHEMOSPHERE
 |
| 出版日期 | 2022-08-01 |
| 卷号 | 301页码:9 |
| ISSN号 | 0045-6535 |
| 关键词 | Metal ions p53 QSAR Genetic toxicity Human health risk |
| DOI | 10.1016/j.chemosphere.2022.134724 |
| 通讯作者 | Wu, Huifeng(hfwu@yic.ac.cn) ; Li, Fei(fli@yic.ac.cn) |
| 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. |
| WOS关键词 | RELATIVE TOXICITY ; IN-VITRO ; CANCER CELLS ; DNA-BINDING ; P53 ; PREDICTION ; QSAR ; DOCKING ; DOMAIN ; WATER |
| WOS研究方向 | Environmental Sciences & Ecology |
| 语种 | 英语 |
| WOS记录号 | WOS:000799858700004 |
| 资助机构 | National Natural Science Foundation of China ; Young Taishan Scholars Program of Shandong Province ; Yantai Science and Technology Development Plan |
| 源URL | [http://ir.yic.ac.cn/handle/133337/31162]  |
| 专题 | 烟台海岸带研究所_中科院海岸带环境过程与生态修复重点实验室 烟台海岸带研究所_近岸生态与环境实验室 |
| 通讯作者 | Wu, Huifeng; Li, Fei |
| 作者单位 | 1.Chinese Acad Sci, Ctr Ocean Mega Sci, Qingdao 266071, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Fisheries Sci & Food Prod Proc, Qingdao 266237, Peoples R China 4.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 |
| 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. |
入库方式： OAI收割
来源：烟台海岸带研究所
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