Mechanisms of tetraethylammonium ion block in the KcsA potassium channel

FEBS Letters
Victor B Luzhkov, J Aqvist

Abstract

We report results from automated docking and microscopic molecular dynamics simulations of the tetraethylammonium (TEA) complexes with KcsA. Binding modes and energies for TEA binding at the external and internal sides of the channel pore are examined utilising the linear interaction energy method. Effects of the channel ion occupancy (based on our previous results for the ion permeation mechanisms) on the binding energies are considered. Calculations show that TEA forms stable complexes at both the external and internal entrances of the selectivity filter. Furthermore, the effects of the Y82V mutation are evaluated and the results show, in agreement with experimental data, that the mutant has a significantly reduced binding affinity for TEA at the external binding site, which is attributed to stabilising hydrophobic interactions between the ligand and the tyrosines.

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Citations

Oct 29, 2003·Biochimica Et Biophysica Acta·Victor B LuzhkovJohan Aqvist
Mar 17, 2004·Bioorganic & Medicinal Chemistry·Natalia Pérez-HernándezJulio D Martín
Apr 18, 2002·Current Opinion in Structural Biology·Benoît Roux
Aug 7, 2003·Bioorganic & Medicinal Chemistry·Karolina ErsmarkAnders Hallberg
Oct 6, 2012·Chemical Reviews·Christopher MaffeoAleksei Aksimentiev
Apr 27, 2005·Nature Structural & Molecular Biology·Michael J LenaeusAdrian Gross
Jul 30, 2003·The Journal of General Physiology·Jill Thompson, Ted Begenisich
Feb 26, 2004·The Journal of General Physiology·Froylan Gómez-LagunasLourival D Possani
Nov 30, 2006·The Journal of General Physiology·Christopher A AhernRichard Horn
Nov 30, 2006·The Journal of General Physiology·Benoît Roux
Mar 28, 2012·The Journal of General Physiology·Qiulin TanLi-Qun Gu
Apr 12, 2003·The Japanese Journal of Physiology·Hirofumi ShimizuShigetoshi Oiki
Mar 31, 2016·Cell Chemical Biology·Firdaus SamsudinPhilip W Fowler
Mar 4, 2015·Molecular Pharmaceutics·Christian JorgensenCarmen Domene
Oct 10, 2014·Journal of Chemical Information and Modeling·Tobias LinderAnna Stary-Weinzinger
Feb 1, 2005·Biochimica Et Biophysica Acta·V B Luzhkov, J Aqvist
May 24, 2006·Biophysical Chemistry·Tomás HrobárikPavel Jungwirth
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