糖原合成酶激酶3β活性调节机制的分子动力学模拟

摘要

Objective: To study the regulative mechanism of glycogen synthase kinase-3β (GSK-3β) activity. Methods: GSK-3β-Axin complex and GSK-3β-FRATtide complex were modeled by molecular dynamics (MD) simulations using Desmond 9.0 software. Results: In GSK-3β-FRATtide complex, the hydrogen bonds between Lys205 and Glu211, Asn213 were disappeared, the salt bridge between Lys205 and Glu211 were disappeared. Besides, Arg219 of FRATtide and Asp264 of GSK-3β, Gly259 and Arg220 of GSK-3β could form hydrogen bonds. Furthermore, Phe67 and Phe93 exhibited positional shifts. All of these would lead to the conformational changes of the activation loop of GSK-3β, which would inhibit GSK-3β catalytic activity by FRATtide. Conclusion: GSK-3β regulates its catalytic activity by changing the conformation of the activation loop.%目的:探讨研究糖原合成酶激酶(GSK-3β)的活性调节机制.方法:利用Desmond 9.0软件对GSK-3β-轴素复合物和GSK-3β-FRATtide复合物进行分子动力学模拟研究.结果:与GSK-3β-轴素复合物相比,在GSK-3β-FRATtide复合物中,Lys205同Glu211、Asn213之间的氢键作用消失,Lys205与Glu211不能形成稳定的盐键；FRATtide的Arg219与GSK-3β的Asp264,GSK-3β的Gly259与Arg220之间能形成稳定的氢键.此外,Phe67和Phe93显示出位置的偏移.这些都将导致GSK-3β活性环的构象变化进而抑制GSK-3β的催化活性.结论:GSK-3β的活性调节是通过改变其活化环构象来实现的.