酶活性的分子轨道研究：丝氨酸蛋白酶的催化机制

Molecular orbital studies of enzyme activity: catalytic mechanism of serine proteinases.

作者信息

Scheiner S, Lipscomb W N

出版信息

Proc Natl Acad Sci U S A. 1976 Feb;73(2):432-6. doi: 10.1073/pnas.73.2.432.

DOI:10.1073/pnas.73.2.432

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC335923/

Abstract

The catalytic activity of the serine proteinases is studied using molecular orbital methods on a model of the enzyme-substrate complex. A mechanism is employed in which Ser-195, upon donating a proton to the His-57-Asp-102 dyad, attacks the substrate to form the tetrahedral intermediate. As His-57 then donates a proton to the leaving group, the intermediate decomposes to the acyl enzyme. An analogous process takes place during deacylation, as a water molecule takes the place of Ser-195 as the nucleophile. The motility of the histidine is found to be an important factor in both steps. An attempt is made to include the effects of those atoms not explicitly included in the calculations and to compare the reaction rate of the proposed mechanism with that of the uncatalyzed hydrolysis. This mechanism is found to be in good agreement with structural and kinetic data.

摘要

利用分子轨道方法，在酶 - 底物复合物模型上研究了丝氨酸蛋白酶的催化活性。采用了一种机制，其中Ser - 195在将质子给予His - 57 - Asp - 102二元组后，攻击底物形成四面体中间体。随后His - 57将质子给予离去基团，中间体分解为酰基酶。在脱酰基过程中发生类似的过程，因为水分子取代Ser - 195作为亲核试剂。发现组氨酸的移动性在这两个步骤中都是一个重要因素。尝试纳入计算中未明确包含的那些原子的影响，并将所提出机制的反应速率与未催化水解的反应速率进行比较。发现该机制与结构和动力学数据高度吻合。

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