A Buried Water Molecule Influences Reactivity in α-Amylase on a Subnanosecond Time Scale
| Autor: | Ana R. Calixto, Maria J. Ramos, Diogo Santos-Martins, Pedro A. Fernandes |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
chemistry.chemical_classification
010304 chemical physics Hydrogen bond Substrate (chemistry) Glycosidic bond General Chemistry 010402 general chemistry 01 natural sciences Catalysis 0104 chemical sciences Reaction coordinate Molecular dynamics Crystallography chemistry 0103 physical sciences Molecule Reactivity (chemistry) |
| Zdroj: | ACS Catalysis. 8:4055-4063 |
| ISSN: | 2155-5435 |
| DOI: | 10.1021/acscatal.7b04400 |
| Popis: | The subset of catalytically competent conformations can be significantly small in comparison with the full conformational landscape of enzyme–substrate complexes. In some enzymes, the probability of finding a reactive conformation can account for up to 4 kcal/mol of activation barrier, even when the substrate remains tightly bound. In this study, we sampled conformations of human pancreatic α-amylase with bound substrate in a molecular dynamics (MD) simulation of over 100 ns and calculated energy profiles along the reaction coordinate. We found that reactive states require a hydrogen bond between a buried water molecule and E233, which is the general acid in the glycolysis mechanism. The effect of this single, nonreactive, intermolecular interaction is as important as the correct positioning and orientation of the reacting residues to achieve a competent energy barrier. This hydrogen bond increases the acidity of E233, facilitating proton transfer to the glycosidic oxygen. In the MD simulation, this requi... |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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