对硝基苯酚降解产物与FK506结合蛋白相互作用分子机制
Molecular mechanism on interaction between p-nitrophenol degradation products and FK506 binding protein
杨传玺 1王小宁 1朱青 2薛岩 3刘琳 1刘永林 1谢康 4陈栋 1孙好芬 1王炜亮1
作者信息
- 1. 青岛理工大学环境与市政工程学院,青岛,266520
- 2. 山东省创新发展研究院,济南,250101
- 3. 青岛理工大学管理工程学院,青岛,266520
- 4. 济南大学土木建筑学院,济南,250022
- 折叠
摘要
对硝基苯酚(p-nitrophenol,p-NP)作为典型内分泌干扰物,其环境污染与人体健康问题一直是环境领域的研究热点.环境中对硝基苯酚降解产物(p-NP degradation products,p-NP-DPs)与FK506结合蛋白(FK506 binding protein,FKBP5)结合形成p-NP-DPs-FKBP5加合物是p-NP-DPs产生雌激素和抗雄激素活性的主要机制.然而,p-NP-DPs与FKBP5相互作用的分子水平机制尚未引起足够的重视.本文采用分子对接技术模拟计算p-NP-DPs与FKBP5相互作用的结合能和结合面积.结果表明,p-NP-DPs与FKBP5相互作用结合面积顺序为213 Å2(4-硝基邻苯二酚)＞200 Å2(p-NP)＞184 Å2(邻苯二酚)＞175 Å2(对苯二酚)＞173 Å2(苯酚)＞171 Å2(对苯醌),结合能顺序为-3.69 kcal mol-1(4-硝基邻苯二酚)＞-3.76 kcal·mol-1(p-NP)＞-3.81 kcal·mol-1(对苯二酚/邻苯二酚)＞-3.83 kcal mol-1(对苯醌)＞-3.91 kcal·mol-1(苯酚),高频氨基酸残基为 Pro221、Gly224、Glu227、Ala228、Gly282、Lys283、Tyr284、Met285和Gln286,p-NP-DPs药效团主要包括氢键供体(—OH)、氢键受体(—NO2和C=O)、芳香中心(苯环)和疏水中心(C原子).p-NP-DPs理化性质对p-NP-DPs与FKBP5相互作用强度的影响主要取决于分子量和拓扑极表面积(100％)、氢键受体数量(75％)、密度(50％)和闪点(25％).本研究对认识水环境中p-NP-DPs分子水平健康效应和环境风险具有重要科学意义.
Abstract
P-nitrophenol(p-NP),as typical endocrine disruption chemicals(EDCs),their environmental pollution and human health issues have always been hotspots in the environmental field.The p-NP-DPs-FKBP5 adducts,formed by p-NP degradation products(p-NP-DPs)and FK506 binding protein(FKBP5),is the main estrogenic and anti-androgenic mechanism.However,this molecular-level mechanism between p-NP-DPs and FKBP5 has not attracted enough attention.In this study,the molecular docking technology was used to simulate the binding energy and binging area between p-NP-DPs and FKBP5 interaction.The results indicated that the order of binging area between p-NP-DPs and FKBP5 interaction was 213 Å2(4-nitrocatechol)＞200 Å2(p-NP)＞184 Å2(o-dihydroxybenzene)＞175 Å2(p-dihydroxybenzene)＞173 Å2(phenol)＞171 Å2(p-benzoquinone),but the order of binding energy between p-NP-DPs and FKBP5 interaction was-3.69 kcal·mol-1(4-nitrocatechol)＞-3.76kcal·mol-1(p-NP)＞-3.81 kcal·mol-1(p-/o-dihydroxybenzene)＞-3.83 kcal·mol-1(p-benzoquinone)＞-3.91 kcal·mol-1(phenol).The high frequency amino acid residues were included Pro221,Gly224,Glu227,Ala228,Gly282,Lys283,Tyr284,Met285 and Gln286.The pharmacophores of p-NP-DPs were included hydrogen-bond donor(—OH),hydrogen-bond acceptor(—NO2 and C=O),aromatic center(benzene ring)and hydrophobic center(C atom).The physicochemical properties of p-NP-DPs were dependent on molecular weight and topological polar surface area(100％),hydrogen bond donor count(75％),density(50％)and flash point(25％).The research results probably enhance people's knowledge and understanding of molecular-level health effects and environmental risks of p-NP-DPs in the water environmental system in the future.
关键词
对硝基苯酚/FK506结合蛋白/分子对接/药效团/构效关系Key words
p-NP/FKBP5/molecular docking/pharmacophore/structure-activity relationship引用本文复制引用
基金项目
国家自然科学基金(42207019)
国家自然科学基金(41672340)
出版年
2024
NETL
NSTL
万方数据