Parametrisation of the free energy of ATP binding to wild-type and mutant Kir6.2 potassium channels
| Autor: | Oscar Moran, Paolo Tammaro, Alessandro Grottesi, Andrew J. Chadburn |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
endocrine system
ATP-sensitive potassium channel Molecular Sequence Data Biophysics Biochemistry Adenosine Triphosphate ATP synthase gamma subunit Animals Amino Acid Sequence Potassium Channels Inwardly Rectifying Binding site Binding Sites biology Chemistry Organic Chemistry Wild type Kir6.2 Potassium channel Rats Molecular Docking Simulation Structural Homology Protein Docking (molecular) Mutation biology.protein cardiovascular system Thermodynamics Sequence Alignment ATP synthase alpha/beta subunits |
| Zdroj: | Biophysical chemistry 171 (2013): 76–83. doi:10.1016/j.bpc.2012.10.006 info:cnr-pdr/source/autori:Moran O, Grottesi A, Chadburn AJ, Tammaro P./titolo:Parametrisation of the free energy of ATP binding to wild-type and mutant Kir6.2 potassium channels/doi:10.1016%2Fj.bpc.2012.10.006/rivista:Biophysical chemistry (Print)/anno:2013/pagina_da:76/pagina_a:83/intervallo_pagine:76–83/volume:171 |
| ISSN: | 1873-4200 0301-4622 |
| Popis: | ATP-sensitive K+ (KATP) channels, comprised of pore-forming Kir6.x and regulatory SURx subunits, play important roles in many cellular functions; because of their sensitivity to inhibition by intracellular ATP, KATP channels provide a link between cell metabolism and membrane electrical activity. We constructed structural homology models of Kir6.2 and a series of Kir6.2 channels carrying mutations within the putative ATP-binding site. Computational docking was carried out to determine the conformation of ATP in its binding site. The Linear Interaction Energy (LIE) method was used to estimate the free-energy of ATP binding to wild-type and mutant Kir6.2 channels. Comparisons of the theoretical binding free energies for ATP with those determined from mutational experiments enabled the identification of the most probable conformation of ATP bound to the Kir6.2 channel. A set of LIE parameters was defined that may enable prediction of the effects of additional Kir6.2 mutations within the ATP binding site on the affinity for ATP. |
| Databáze: | OpenAIRE |
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