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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.
- 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.)
- Subjects :
- Algorithms
Amides chemistry
Animals
Binding Sites
Binding, Competitive
Cell Line, Tumor
Cell Proliferation drug effects
Cells, Cultured
Cnidarian Venoms chemistry
Cnidarian Venoms metabolism
Dose-Response Relationship, Drug
Humans
Ion Channel Gating genetics
Ion Channel Gating physiology
Kv1.1 Potassium Channel genetics
Kv1.1 Potassium Channel metabolism
Kv1.1 Potassium Channel physiology
Kv1.3 Potassium Channel genetics
Kv1.3 Potassium Channel metabolism
Mice
Models, Molecular
Molecular Dynamics Simulation
Patch-Clamp Techniques
Potassium Channel Blockers chemistry
Potassium Channel Blockers metabolism
Protein Binding
Protein Structure, Tertiary
T-Lymphocytes cytology
T-Lymphocytes drug effects
Cnidarian Venoms pharmacology
Ion Channel Gating drug effects
Kv1.3 Potassium Channel physiology
Potassium Channel Blockers pharmacology
Subjects
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