蛋白酪氨酸磷酸酯酶1B活性位点Asp 48突变理论研究  

Theoretical studies on point mutations of Asp 48 in the active site of protein tyrosine phosphatease 1B

作　　者：刘桂友[1] 刘梦源[1] 王润玲[1] 程先超[1] 周慧[1] 谢宪斌[1] 

机构地区：[1]天津医科大学药学院,天津300070

出　　处：《天津医科大学学报》2009年第4期562-565,共4页Journal of Tianjin Medical University

摘　　要：目的:利用点突变研究PTP1B中Asp 48的重要性。方法:理论研究采用分子力学原理,使用HyperChem 7.0的AMBER99力场。首先对PTP1B中Asp 48进行点突变,然后利用Polak-Ribiere共轭梯度法对复合物结构进行优化。计算优化结构的静电相互作用能、范德华相互作用能、二面角等指标,并通过比较突变后这些指标的变化,分析酶与底物的相互作用变化。结果:突变后活性位点的形状、PTP1B的空间构象及底物与催化相关残基的相互作用能均未发生显著变化。而D48K、D48I和D48T则导致底物与非催化相关残基的相互作用降低。结论:点突变对活性位点的形状、PTP1B的空间构象和催化活性的影响较小,但D48K、D48I和D48T会导致底物与PTP1B的结合能力下降。Objective： To investigate the importance of Asp 48 contributed to catalysis in PTP1B by means of point mutation. Methods： Theoretical studies were carried out using molecular mechanics with an AMBER99 force field from the HyperChem7.0 program, Asp 48 were mutated and the complex structures were optimized with energy minimization using Polak-Ribiere conjugate gradient method. The electrostatic interaction energies, van der Waals interaction energies, dihedral angles were calculated as descriptors to identify the interaction change between the substrate and enzyme after mutation. Results： No significant change was found on the shape of active site, conformation of PTP1B and the interaction energies of substrate with catalytic residues after mutations. But D48K, D48I and D48T lead to reduced interaction energies between substrate and residues which do not participate catalysis. Conclusion： Point mutations have little influence on the shape of active site, conformation of PTP1B and catalytic activity. But D48K, D48I and D48T lead to decreased binding affinity.

关 键 词：蛋白酪氨酸磷酸酯酶1B 突变 分子力学 

分 类 号：R9[医药卫生—药学] Q7[生物学—分子生物学]