钠-葡萄糖转运蛋白2的同源模建研究

Study on homology modeling of sodium glucose co-transporter protein 2

钠-葡萄糖转运蛋白2(SGLT2)是一类介导肾脏葡萄糖重吸收的葡萄糖转运蛋白,其抑制剂可减少葡萄糖的重吸收,促进尿液中葡萄糖的排泄,有效降低血糖水平,被认为是糖尿病治疗的新靶点。目前尚无可用的SGLT2晶体结构,这极大地限制了从天然活性物质中筛选和开发SGLT2抑制剂。运用计算机辅助药物设计的方法,通过同源模建对SGLT2的三维结构进行模拟,采用拉氏图、分子对接以及与实验活性对比等方法对模型质量进行评估。结果表明,所构建的SGLT2三维模型合理、可靠,可用于开展基于结构的虚拟筛选,或为开发新型、高效、安全的非糖苷类SGLT2抑制剂提供参考。

Sodium glucose co-transporter protein 2(SGLT2) is a kind of glucose transporter proteins involved in renal glucose reabsorption. SGLT2 inhibitors can reduce the glucose reabsorption, promote the excretion of glucose in the urine, and effectively reduce the blood glucose level, which considered as the new target for the treatment of diabetes. However, there is no available crystal structure of SGLT2, which greatly limits the screening and development of SGLT2 inhibitors from natural products. In this study, the computer-aided drug design was used to build the three dimensional structure of SGLT2 by homologous modeling. The quality of the three dimensional structure model of SGLT2 was evaluated by means of Ramachandran plot, molecular docking and comparison of experimental activity. The results showed that the established three dimensional structure model of SGLT2 was reasonable and reliable, and could be used to carry out structure-based virtual screening, which may provide reference for the development of new, efficient and safe non-glycoside SGLT2 inhibitors.