人酪氨酸酶的同源模建研究

Homology Modeling of Human Tyrosinase

酪氨酸酶是皮肤黑色素生物合成过程中的限速酶,其抑制剂作为皮肤脱色剂具有重要的商业价值.目前尚无可用的人酪氨酸酶晶体结构,极大地限制了人酪氨酸酶抑制剂的研究.以人酪氨酸酶相关蛋白-1的晶体结构为模板,利用同源模建法对人酪氨酸酶的三维结构进行了模拟,采用分子对接对曲酸与人源模型和蘑菇酪氨酸酶的结合模式进行比较.随后采用分子动力学方法获得了稳定的复合物结构以获得更详细的信息.该研究为接下来的人酪氨酸酶抑制剂的虚拟筛选打下了基础,也为基于曲酸结构开发更高效的人酪氨酸酶抑制剂提供了思路.

Tyrosinase is responsible for the rate-limiting step in melanin synthesis in mammalian skin.Potent human tyrosinase inhibitors are of important commercial value as a skin-depigmenting agent.So far,no crystal structure for full length human tyrosinase is available,which hinders the study of human tyrosinase inhibitors.In this study,a homology model of the 3 D structure of human tyrosinase was built by means of the homology modeling method.The recently obtained crystal structure of human tyrosinase-related protein-1,which has high identity(40%)to the human enzyme,was used as the template.The molecular docking approach was employed to compare the binding modes of kojic acid with those of human enzyme and mushroom tyrosinase.Then,the molecular dynamics method was used to obtain the stable structure of the complex for more detailed information.It is estimated that this research lays a foundation for further virtual screening for human tyrosinae inhibitors and provides useful information to modify the structure of kojic acid for the development of more potent human tyrosinase inhibitors.