CAJ | 학술논문

细胞色素P450(CYP)2E1家族酶是一种具有双重功能的单加氧酶，能够参与市场上6%药物的代谢而具有重要的作用。这类酶与酒精的消耗、糖尿病、肥胖症以及厌食症等密切相关，引起了广泛的研究兴趣。目前尚未见从原子水平上对这种酶在不同乙醇浓度下构象行为的研究。基于此，本文研究了花生四烯酸(AA)与CYP2E1复合物结构在不同乙醇浓度下构象与能量变化的特点。对于在不同乙醇浓度下 AA 与CYP2E1的复合物结构，采用分子动力学模拟结合自由能计算的方法进行研究。分子动力学模拟结果表明， His109和Lys243氨基酸残基对AA与CYP2E1的结合起到了至关重要的作用。当体系的乙醇浓度较高时， AA的结合能力有所下降，这种结合能力的下降是由于AA与CYP2E1之间氢键相互作用力的减弱所致。本研究对于AA与CYP2E1复合物结构在不同乙醇浓度下， AA分子与CYP2E1分子结合能力下降以及CYP2E1的构象变化给出了详细的解释。本研究工作得到的结论对于实验和理论研究均有重要意义，可为后续细胞色素P450酶类催化活性的研究提供理论支持。
세포색소P450(CYP)2E1가족매시일충구유쌍중공능적단가양매，능구삼여시장상6%약물적대사이구유중요적작용。저류매여주정적소모、당뇨병、비반증이급염식증등밀절상관，인기료엄범적연구흥취。목전상미견종원자수평상대저충매재불동을순농도하구상행위적연구。기우차，본문연구료화생사희산(AA)여CYP2E1복합물결구재불동을순농도하구상여능량변화적특점。대우재불동을순농도하 AA 여CYP2E1적복합물결구，채용분자동역학모의결합자유능계산적방법진행연구。분자동역학모의결과표명， His109화Lys243안기산잔기대AA여CYP2E1적결합기도료지관중요적작용。당체계적을순농도교고시， AA적결합능력유소하강，저충결합능력적하강시유우AA여CYP2E1지간경건상호작용력적감약소치。본연구대우AA여CYP2E1복합물결구재불동을순농도하， AA분자여CYP2E1분자결합능력하강이급CYP2E1적구상변화급출료상세적해석。본연구공작득도적결론대우실험화이론연구균유중요의의，가위후속세포색소P450매류최화활성적연구제공이론지지。
Cytochrome P450(CYP) 2E1 is a dual function monoxygenase with a crucial role in the metabolism of 6%of drugs on the market at present. The enzyme is of tremendous interest for its association with alcohol consumption, diabetes, obesity and fasting. The enzyme’ s conformational changes at different ethanol concentrations have not been rationalized at the atomic level. In this regard, we have investigated the effects of different ethanol concentrations on the structural and energetic characteristics upon the complex of arachidonic acid and CYP2E1(AA-CYP2E1). The molecular dynamics(MD) simulation combined with binding free energy calculations was carried out on AA-CYP2E1 complex at different ethanol concentrations. Based on the MD simulation results, two residues, His109 and Lys243, are responsible for the binding of AA molecule. The binding ability of AA molecue is decreased at high concentrations of ethanol. This is due to the loss of certain hydrogen bond interaction. The high concentration of ethanol can also affect the surface structure of AA-CYP2E1. Our work provides detailed atomistic insights into the structure-function <br> relationships of CYP2E1 at different ethanol concentrations under dynamics conditions. This work also provides parti-cular explanations on how different ethanol concentrations affect the surface structure of CYP2E1. Furthermore, the mutational effects on the activity of CYP2E1 obtained in the present study are beneficial to both experiment and com-putation of CYPs and may allow researchers to achieve desirable changes in enzymatic activities.