Exploring the Catalytic Reaction of Cysteine Proteases
| Autor: | Arieh Warshel, Arjun Saha, Gabriel Oanca, Mojgan Asadi, Balajee Ramachandran |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
Reaction mechanism Proteases 010304 chemical physics Chemistry Acylation 010402 general chemistry 01 natural sciences Combinatorial chemistry Catalysis 0104 chemical sciences Surfaces Coatings and Films Kinetics Papain chemistry.chemical_compound Energy profile Enzyme Cysteine Proteases 0103 physical sciences Materials Chemistry Physical and Theoretical Chemistry Cysteine |
| Zdroj: | The Journal of Physical Chemistry B. 124:11349-11356 |
| ISSN: | 1520-5207 1520-6106 |
| Popis: | Cysteine proteases play a major role in many life processes and are the target of key drugs. The reaction mechanism of these enzymes is a complex process, which involves several steps that are divided into two main groups: acylation and deacylation. In this work, we studied the energy profile for the acylation and a part of the deacylation reaction of three different enzymes, cruzain, papain, and the Q19A-mutated papain with the benzyloxycarbonyl-phenylalanylarginine-4-methylcoumaryl-7-amide (CBZ-FR-AMC) substrate. The calculations were performed using the EVB and PDLD/S-LRA methods. The overall agreement between the calculated and observed results is encouraging and indicates that we captured the correct reaction mechanism. Finally, our finding indicates that the minimum of the reaction profile, between the acylation and deacylation steps, should provide an excellent state for the binding of covalent inhibitors. |
| Databáze: | OpenAIRE |
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