摘要
【目的】构建漆酶-介质-有机磷酸酯毒物三元复合物(laccase-meidator-organophosphate poison ternary complex,LMO)模型,在分子水平探究漆酶-介质体系(laccase-mediator system,LMS)对有机磷酸酯毒物(organophosphate poisons,OPs)的降解机制。【方法】基于分子对接建立LMO模型,通过分子动力学模拟,考察三元体系稳定性和动态研究LMS对OPs的降解机制。【结果】在LMO中,介质结合于漆酶活性位点内部,与Asp206产生氢键作用,与中性氨基酸产生疏水作用和π-π堆积作用;介质首先生成介质中间体,进而与结合于漆酶活性位点外缘的OPs发生相互作用;分子动力学模拟发现,三元复合物达到稳定时漆酶构象发生了突变,电子受体His458远离了Ⅰ型铜离子(type-1 copper ions,T1Cu)。【结论】LMS对OPs的降解是通过漆酶的疏水作用及介质中间体完成的;LMO作用过程中漆酶的构象变化利于促进漆酶与介质间的电子传递,更有利于OPs的降解。
【Objective】The laccase-mediator-organophosphate poison ternary complex（LMO） model was built to investigate the degradation mechanism of organophosphate poisons（OPs） by laccase-mediator system（LMS） on molecular level.【Methods】The ternary complex model was obtained by molecular docking, then, its stability and interaction mechanism were verified using molecular dynamics simulations.【Results】The binding conformation indicates that the mediator at the active site of the laccase interacts with the Asp206 via hydrogen bond, and interacts with neutral amino acid via hydrophobic interaction and π-π accumulation. With the interactions, the mediator translates into free radical, then contacts with the OPs at the edge of the laccase active site. The results of molecular dynamics simulation show that when the ternary complex reach a steady conformation, the His 458 at the active site stands off the type-1 copper ions.【Conclusions】The conformation transition of laccase promotes the electron transfer between laccase and substrate. The degradation of OPs is caused directly by the mediator free radical binding at the laccase active site.
出处
《武警后勤学院学报（医学版）》
CAS
2017年第5期387-391,共5页
Journal of Logistics University of PAP（Medical Sciences）
基金
武警后勤项目(WJHQ2012-14)
武警后勤学院重点项目(WHZ201201)
武警后勤学院基础研究项目(WHJ2016025)
武警后勤学院研究生创新课题(WHYC201603)
天津市卫生局科技基金(2015KZ123)
关键词
漆酶
介质
有机磷酸酯毒物
分子对接
分子动力学模拟
分子机制
Laccase
Mediator
Organophosphate poisons
Molecular docking
Molecular dynamics simulation
Interaction mechanism
