Mechanisms of tetraethylammonium ion block in the KcsA potassium channel

被引:76
作者
Luzhkov, VB [1 ]
Åqvist, J [1 ]
机构
[1] Uppsala Univ, Dept Cell & Mol Biol, S-75124 Uppsala, Sweden
关键词
potassium channel; KcsA; block; tetraethylammonium; binding site; linear interaction energy method;
D O I
10.1016/S0014-5793(01)02381-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:191 / 196
页数:6
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