Effects of Osmolytes on Ligand Binding to Dihydropteroate Synthase from Bacillus anthracis
| Autor: | Elizabeth E. Howell, Deepika Nambiar, Michael R. Duff, Ojaswini Sharma |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
010304 chemical physics Osmotic shock 010402 general chemistry Ligand (biochemistry) 01 natural sciences Pyrophosphate Trehalose 0104 chemical sciences Surfaces Coatings and Films chemistry.chemical_compound Enzyme chemistry Osmolyte 0103 physical sciences Materials Chemistry Biophysics Proline Physical and Theoretical Chemistry Pterin |
| Zdroj: | The Journal of Physical Chemistry B. 124:6212-6224 |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/acs.jpcb.0c03311 |
| Popis: | Osmolyte interactions with ligands can affect their affinity for proteins and are dependent upon the cosolute and the functional groups of the ligand. Here, we explored ligand binding to Bacillus anthracis dihydropteroate synthase (BaDHPS) under osmotic stress conditions. Osmolyte effects were specific to the cosolute and ligand, suggesting interaction of the osmolytes with the free ligands in solution. The association rates of pterin pyrophosphate were mostly unaffected by the osmolytes, except for a 2-fold decrease in the presence of 1 M trehalose, while the dissociation rates decreased in most osmolyte solutions. The viscosity and dielectric constant of the solution did not correlate with the effects of the osmolytes. Experimental results were compared with predicted preferential interaction coefficients (Δμ23/RT) between the osmolytes and ligands. The Δμ23/RT were able to predict the experimental data for most of the osmolytes. Trehalose and proline effects did not correlate with the predicted values, indicating that these two osmolytes may affect binding in more complex ways than simple preferential interactions. Additionally, osmolytes weakly interacted with the sulfa drug sulfathiazole, which altered its affinity for BaDHPS, suggesting that these types of weak interactions can also impact drug binding. As osmolytes affect ligands binding to two different folate cycle enzymes (DHFRs and DHPS), we predicted how ligand binding to other folate cycle enzymes will be altered by the presence of osmolytes. |
| Databáze: | OpenAIRE |
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