丝氨酸蛋白酶催化机制的量子化学研究(Ⅰ)

A Quantum Chemical Study on The Catalytic Mechanism of Serine Proteases(Ⅰ)

用半经验的MNDO/H法对在丝氨酸蛋白酶的活性中心形成四面中间体模拟反应的几个系统进行了研究。讨论了“催化三联体”各组份对增加丝氨酸羟基反应能力所起的作用。表明His和Asp间形成了强氢键,对降低丝氨酸和底物反应的活化能是重要的。分析了Ser和His、His和Asp间质子位置变化。考虑了底物变形对中间体形成能量的影响。

Using the semi-empirical MNDO/H method several systems simulating the reaction of tetrahetral intermediate formation in the active site of serine proteases have been studied. The role played by elements of the《catalytic triad》in increasing the reactivity of serine hydroxyl has been discussed.The formation of a strong hydrogen bond between His and Asp was shown to be important in lowering the activation energy in the reaction of Ser with substrate.The change in position of the proten located between Ser and His and between His and Asp was analysed.The influence of substrate distortion on the energy of intermediate formation has been considered.