Molecular orbital studies of enzyme activity: catalytic mechanism of serine proteinases.
Molecular orbital studies of enzyme activity: catalytic mechanism of serine proteinases.
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酶活性的分子轨道研究：丝氨酸蛋白酶的催化机制。
DOI：
10.1073/pnas.73.2.432
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发表时间：
1976
影响因子：
11.1
通讯作者：
W. Lipscomb
中科院分区：
文献类型：
--
作者：
S. Scheiner;W. Lipscomb
丝氨酸蛋白酶的催化活性的研究使用分子轨道方法上的酶-底物复合物的模型。采用了一种机制，其中Ser-195在向His-57-Asp-102二联体提供质子后攻击底物以形成四面体中间体。由于His-57随后向离去基团提供质子，中间体分解为酰基酶。在脱酰化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。组氨酸的运动被认为是在这两个步骤中的一个重要因素。尝试包括那些原子的影响，没有明确包括在计算中，并比较所提出的机制与非催化水解的反应速率。这种机制被认为是在良好的协议与结构和动力学数据。
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.