A drug pocket at the lipid bilayer–potassium channel interface | Zendy

Nina E. Ottosson | Zendy; Malin Silverå Ejneby | Zendy; Xiongyu Wu | Zendy; Samira Yazdi | Zendy; Peter Konradsson | Zendy; Erik Lindahl | Zendy; Fredrik Elinder | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

A drug pocket at the lipid bilayer–potassium channel interface

Author(s) -

Nina E. Ottosson,

Malin Silverå Ejneby,

Xiongyu Wu,

Samira Yazdi,

Peter Konradsson,

Erik Lindahl,

Fredrik Elinder

Publication year - 2017

Publication title -

science advances

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.928

H-Index - 146

ISSN - 2375-2548

DOI - 10.1126/sciadv.1701099

Subject(s) - lipid bilayer , bilayer , potassium channel , interface (matter) , biophysics , channel (broadcasting) , chemistry , voltage gated potassium channel , nanotechnology , molecule , materials science , membrane , biochemistry , computer science , biology , computer network , organic chemistry , gibbs isotherm

Many pharmaceutical drugs against neurological and cardiovascular disorders exert their therapeutic effects by binding to specific sites on voltage-gated ion channels of neurons or cardiomyocytes. To date, all molecules targeting known ion channel sites bind to protein pockets that are mainly surrounded by water. We describe a lipid-protein drug-binding pocket of a potassium channel. We synthesized and electrophysiologically tested 125 derivatives, analogs, and related compounds to dehydroabietic acid. Functional data in combination with docking and molecular dynamics simulations mapped a binding site for small-molecule compounds at the interface between the lipid bilayer and the transmembrane segments S3 and S4 of the voltage-sensor domain. This fundamentally new binding site for small-molecule compounds paves the way for the design of new types of drugs against diseases caused by altered excitability.

Funding Agencies|Swedish Research Council; Swedish Brain Foundation; Swedish Heart-Lung Foundation; Swedish National Infrastructure for Computing

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research