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

作　　者：杨传玺 王小宁 朱青 薛岩 刘琳 刘永林 谢康[4] 陈栋[1] 孙好芬[1] 王炜亮[1] YANG Chuanxi;WANG Xiaoning;ZHU Qing;XUE Yan;LIU Lin;LIU Yonglin;XIE Kang;CHEN Dong;SUN Haofen;WANG Weiliang(School of Environmental and Municipal Engineering,Qingdao University of Technology,Qingdao,266520,China;Shandong Institute of Innovation and Development,Jinan,250101,China;School of Management Engineering,Qingdao University of Technology,Qingdao,266520,China;School of Civil Engineering and Architecture,University of Jinan,Jinan,250022,China)

机构地区：[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

出　　处：《环境化学》2024年第5期1659-1669,共11页Environmental Chemistry

基　　金：国家自然科学基金(42207019,41672340)资助.

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213Å^(2)(4-硝基邻苯二酚)>200Å^(2)(p-NP)>184Å^(2)(邻苯二酚)>175Å^(2)(对苯二酚)>173Å^(2)(苯酚)>171Å^(2)(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(—NO_(2)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.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 213Å^(2)(4-nitrocatechol)>200Å^(2)(p-NP)>184Å^(2)(o-dihydroxybenzene)>175Å^(2)(p-dihydroxybenzene)>173Å^(2)(phenol)>171Å^(2)(p-benzoquinone),but the order of binding energy between p-NP-DPs and FKBP5 interaction was−3.69 kcal·mol^(−1)(4-nitrocatechol)>−3.76 kcal·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(-NO_(2) 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 

分 类 号：X-1[环境科学与工程] O6[理学—化学]