Beneficent and maleficent effects of cations on bufadienolide binding to Na+,K+-ATPase
| Autor: | Lucy Kate Ladefoged, Natalya U. Fedosova, Birgit Schiøtt |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
010304 chemical physics Stereochemistry General Chemical Engineering Kinetics Bufalin General Chemistry Crystal structure Bufadienolide Library and Information Sciences 01 natural sciences 0104 chemical sciences Computer Science Applications 010404 medicinal & biomolecular chemistry chemistry.chemical_compound Transmembrane domain chemistry Docking (molecular) 0103 physical sciences Helix Cardenolide Na+/K+-ATPase Lactone |
| Zdroj: | Ladefoged, L K, Schiøtt, B & Fedosova, N U 2021, ' Beneficent and Maleficent Effects of Cations on Bufadienolide Binding to Na +,K +-ATPase ', Journal of Chemical Information and Modeling, vol. 61, no. 2, pp. 976-986 . https://doi.org/10.1021/acs.jcim.0c01396 Ladefoged, L K, Schiøtt, B & Fedosova, N 2021, ' Beneficent and Maleficent Effects of Cations on Bufadienolide Binding to Na+,K+-ATPase ', Journal of Chemical Information and Modeling, vol. 61, no. 2, pp. 976-986 . https://doi.org/10.1021/acs.jcim.0c01396 |
| DOI: | 10.1101/2020.11.09.373902 |
| Popis: | Kinetic properties and crystal structures of the Na+,K+-ATPase in complex with cardiotonic steroids (CTS) revealed significant differences between CTS subfamilies (Laursen et al., 2015): beneficial effects of K+ on bufadienolide binding strongly contrasted with K+/cardenolide antagonism. To solve this riddle we applied docking and molecular dynamics simulations of the complexes involving Na+,K+-ATPase, bufadienolides (bufalin, cinobufagin), and ions (K+, Na+, Mg2+). The results revealed that bufadienolide binding is affected by i) electrostatic attraction of the lactone ring by a cation, and ii) the ability of a cation to stabilize and “shape” the site constituted by transmembrane helices of the α-subunit (αM1-6). The latter effect was due to varying coordination patterns involving amino acid residues from helix bundles αM1-4 and αM5-10. Substituents on the steroid core of a bufadienolide add to and modify the cation effects. The above rationale is fully consistent with the ion effects on the kinetics of Na+,K+-ATPase/bufadienolide interactions. |
| Databáze: | OpenAIRE |
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