L-缬氨酸对精氨酸酶Ⅰ抑制作用的分子动力学模拟

Molecular Dynamics Simulation of the Inhibition Against Arginase Ⅰ Catalyzed Reaction by L-Val

利用分子动力学模拟与酶学实验相结合的方法,研究了L-缬氨酸(L-Val)对野生型和突变型精氨酸酶Ⅰ的酶促反应动力学的影响.精氨酸酶Ⅰ的活性口袋附近有一个较大的空穴C2,分子动力学模拟结果显示,突变Ile156Arg缩小了空穴C2的容积,而实验结果表明,L-Val对突变型精氨酸酶Ⅰ抑制剂的半抑制浓度(IC_(50))由3.06 mmol/L升高到6.26 mmol/L,增加了1倍,因此精氨酸酶Ⅰ可能存在一个位于空穴C2的调节位点,并且L-Val可以结合于此干扰精氨酸酶Ⅰ的活性.

Molecular dynamics simulation and mutation were used to get the influence at activity and kinetics of enzyme catalyzed reaction by L-Val on W-Arginase Ι and R-Arginase Ι. There is a big cavity C2 near the activity pocket of Arginase Ι. The result of molecular dynamics simulation shows that the mutation of Ile156 Arg narrows the cavity volume of C2. The experimental result shows that influenced by L-Val the half maximal inhibitory concentration（ IC_（50）） of R-Arginase Ι has been risen obviously,the IC_（50） by 3.06 mmol/L rises to6.26 mmol/L. Therefore,Arginase Ι does exist a regulatory site in C2 and L-Val can combine on this site to disturb the activity of Arginase Ι.