细胞松弛素B对葡萄糖/质子共转运蛋白GlcPSe的抑制机理

通过分子动力学对细胞松弛素B与葡萄糖/质子共转运蛋白的两种质子化状态进行了模拟， 发现细胞松弛素B对处于去质子化阶段的葡萄糖转运蛋白具有更好的抑制效果. 结果表明, 357号色氨酸和117号脯氨酸是葡萄糖转运蛋白结合细胞松弛素B的关键氨基酸； 并且当抑制剂与受体蛋白结合时, 位于第10号跨膜螺旋上的357号色氨酸与细胞松弛素B的相对位置对抑制剂的结合有重要意义.

Mechanism of Inhibition of Glucose and Proton Cotransport Protein GlcPSe by Cytochalasin B

Two protonated states of glucose/H⁺ symporter with cytochalasin B were simulated by means of molecular dynamics experiments. It was concluded that cytochalasin B has a better inhibitory effect on glucose transporter proteins in the deprotonation phase. It was found that tryptophan 357 and proline 117 are key amino acids for glucose transporter protein binding to cytochalasin B. Not only that， but when the inhibitor acts， the relative position of tryptophan 357 located on the TM10 to cytochalasin B is important for the binding of the inhibitor. These new findings provide a molecular basis for the understanding of the mechanism of glucose-proton cotransport protein inhibition and the development of drug targets for it.