Investigating the Many Roles of Internal Water in Cytochrome c Oxidase
| Autor: | Alexei A. Stuchebrukhov, Ardavan Farahvash |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Stereochemistry chemistry.chemical_element macromolecular substances Molecular Dynamics Simulation 01 natural sciences Oxygen Respiratory electron transport chain Electron Transport Complex IV 03 medical and health sciences Proton transport 0103 physical sciences Materials Chemistry Molecule Cytochrome c oxidase Physical and Theoretical Chemistry chemistry.chemical_classification 010304 chemical physics biology Chemistry Water Hydrogen Bonding Surfaces Coatings and Films Protein Structure Tertiary 030104 developmental biology Membrane Enzyme Catalytic cycle biology.protein Biocatalysis |
| Zdroj: | The journal of physical chemistry. B. 122(31) |
| ISSN: | 1520-5207 |
| Popis: | Cytochrome c oxidase (C cO) is the terminal enzyme in the respiratory electron transport chain. As part of its catalytic cycle, C cO transfers protons to its Fe-Cu binuclear center (BNC) to reduce oxygen, and in addition, it pumps protons across the mitochondrial inner, or bacterial, membrane where it is located. It is believed that this proton transport is facilitated by a network of water chains inside the enzyme. Here we present an analysis of the hydration of C cO, including the BNC region, using a semi-empirical hydration program, Dowser++, recently developed in our group. Using high-resolution X-ray data, we show that Dowser++ predictions match very accurately the water molecules seen in the D- and K-channels of C cO, as well as in the vicinity of its BNC. Moreover, Dowser++ predicts many more internal water molecules than is typically seen in the experiment. However, no significant hydration of the catalytic cavity in C cO described recently in the literature is observed. As Dowser++ itself does not account for structural changes of the protein, this result supports the earlier assessment that the proposed wetting transition in the catalytic cavity can only either be due to structural rearrangements of BNC, possibly induced by the charges during the catalytic cycle, or occur transiently, in concert with the proton transfer. Molecular dynamics simulations were performed to investigate the global dynamic nature of Dowser++ waters in C cO, and the results suggest a consistent explanation as to why some predicted water molecules would be missing in the experimental structures. Furthermore, in light of the significant protein hydration predicted by Dowser++, the dielectric constant of the hydrated cavities in C cO was also investigated using the Fröhlich-Kirkwood model; the results indicate that in the cavities where water is packed sufficiently densely the dielectric constant can approach values comparable even to that of bulk water. |
| Databáze: | OpenAIRE |
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