State Key Laboratory of Pollutant Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210046, People's Republic of China.
Ecotoxicology. 2011 Jul;20(5):1041-6. doi: 10.1007/s10646-011-0643-z. Epub 2011 Mar 22.
Cytochrome P450 2E1 (CYP2E1) is a cytochrome P450 enzyme involved in styrene metabolism. This study compared the binding affinities between styrene and 11 mammalian CYP2E1 systems using bioinformatics methods. Firstly, amino acid sequences of CYP2E1s were obtained from the Swiss-Prot database. Then, taking the crystal structure of human CYP2E1 as a template, 3D models of the CYP2E1s of other mammals were constructed using the SWISS-MODEL program. Finally, the generated homology models were applied to calculate their docking capacities against styrene and polystyrene using the Surflex-Dock program, which could automatically dock ligands into a receptor's ligand binding site using a protomol based approach and assess the affinity by an empirically derived scoring function. Docking experiments showed that the studied mammalian CYP2E1s had high binding affinities with styrene. For polystyrene, the dimmer of styrene has high binding affinities with CYP2E1s, however, trimer and other high polymers were found hard to be docked into the CYP2E1s. The results of this study indicated that bioinformatics approaches might be useful tools to predict styrene and polystyrene affinities with mammalian CYP2E1s.
细胞色素 P450 2E1（CYP2E1）是一种参与苯乙烯代谢的细胞色素 P450 酶。本研究采用生物信息学方法比较了苯乙烯与 11 种哺乳动物 CYP2E1 系统之间的结合亲和力。首先，从 Swiss-Prot 数据库中获取 CYP2E1 的氨基酸序列。然后，以人 CYP2E1 的晶体结构为模板，使用 SWISS-MODEL 程序构建其他哺乳动物 CYP2E1 的 3D 模型。最后，使用 Surflex-Dock 程序计算生成的同源模型对苯乙烯和聚苯乙烯的对接能力，该程序可以使用基于原型分子的方法自动将配体对接入受体的配体结合位点，并通过经验衍生的评分函数评估亲和力。对接实验表明，所研究的哺乳动物 CYP2E1 与苯乙烯具有很高的结合亲和力。对于聚苯乙烯，苯乙烯的二聚体与 CYP2E1 具有很高的结合亲和力，然而，三聚体和其他高聚物则难以对接进入 CYP2E1。本研究结果表明，生物信息学方法可能是预测苯乙烯和聚苯乙烯与哺乳动物 CYP2E1 亲和力的有用工具。
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