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A C-terminally amidated analogue of ShK is a potent and selective blocker of the voltage-gated potassium channel Kv1.3.

A C-terminally amidated analogue of ShK is a potent and selective blocker of the voltage-gated potassium channel Kv1.3.

Authors :
Pennington MW
Harunur Rashid M
Tajhya RB
Beeton C
Kuyucak S
Norton RS
Source :
FEBS letters [FEBS Lett] 2012 Nov 16; Vol. 586 (22), pp. 3996-4001. Date of Electronic Publication: 2012 Oct 09.
Publication Year :
2012

Abstract

ShK, a 35-residue peptide from a sea anemone, is a potent blocker of potassium channels. Here we describe a new ShK analogue with an additional C-terminus Lys residue and amide. ShK-K-amide is a potent blocker of Kv1.3 and, in contrast to ShK and ShK-amide, is selective for Kv1.3. To understand this selectivity, we created complexes of ShK-K-amide with Kv1.3 and Kv1.1 using docking and molecular dynamics simulations, then performed umbrella sampling simulations to construct the potential of mean force of the ligand and calculate the corresponding binding free energy for the most stable configuration. The results agree well with experimental data.<br /> (Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1873-3468
Volume :
586
Issue :
22
Database :
MEDLINE
Journal :
FEBS letters
Publication Type :
Academic Journal
Accession number :
23063513
Full Text :
https://doi.org/10.1016/j.febslet.2012.09.038