A C-terminally amidated analogue of ShK is a potent and selective blocker of the voltage-gated potassium channel Kv1.3
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.
- Publication:
-
FEBS Letters
- Pub Date:
- November 2012
- DOI:
- 10.1016/j.febslet.2012.09.038
- Bibcode:
- 2012FEBSL.586.3996P
- Keywords:
-
- TEM;
- effector memory T-cells;
- Kv;
- voltage-gated K+ channel;
- ShK;
- K+ channel toxin from Stichodactyla helianthus;
- ShK-amide;
- C-terminally amidated ShK;
- ShK-K-amide;
- ShK with a C-terminal Lys and amide;
- MD;
- molecular dynamics;
- PMF;
- potential of mean force;
- ShK;
- C-terminal amide;
- Potassium channel;
- Electrophysiology;
- Potential of mean force;
- Umbrella sampling