期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1976
卷号：73
期号：2
页码：432-436
DOI：10.1073/pnas.73.2.432
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
