Mechanisms of tetraethylammonium ion block in the KcsA potassium channel

FEBS Letters

Åqvist, Johan¹  Luzhkov, Victor B¹ 

[1] Department of Cell and Molecular Biology, Uppsala University, BMC, Box 596, S-751 24 Uppsala, Sweden

关键词: Potassium channel;    KcsA;    Block;    Tetraethylammonium;    Binding site;    Linear interaction energy method;   

DOI  :  10.1016/S0014-5793(01)02381-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown