Catalytic Mechanism of Serine Proteinases
Document Type
Article
Journal/Book Title
Proceedings of the National Academy of Sciences
Publication Date
2-1976
Publisher
National Academy of Sciences
Volume
73
Issue
2
First Page
432
Last Page
436
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.
Recommended Citation
Scheiner, Steve and Lipscomb, W. N., "Catalytic Mechanism of Serine Proteinases" (1976). Chemistry and Biochemistry Faculty Publications. Paper 578.
https://digitalcommons.usu.edu/chem_facpub/578
