Identifying regulators for EAG1 channels with a novel electrophysiology and tryptophan fluorescence based screen

Ether-à-go-go (EAG) channels are expressed throughout the central nervous system and are also crucial regulators of cell cycle and tumor progression. The large intracellular amino- and carboxy- terminal domains of EAG1 each share similarity with known ligand binding motifs in other proteins, yet EAG...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2010-09, Vol.5 (9), p.e12523
Main Authors: Brelidze, Tinatin I, Carlson, Anne E, Davies, Douglas R, Stewart, Lance J, Zagotta, William N
Format: Article
Language:English
Subjects:
Animals
Benzofuran
Binding
Biochemistry/Biomacromolecule-Ligand Interactions
Biochemistry/Experimental Biophysical Methods
Biophysics
Biophysics/Biomacromolecule-Ligand Interactions
Biophysics/Experimental Biophysical Methods
Cancer
Cardiovascular disease
Cell cycle
Central nervous system
Drosophila
Drug discovery
Drug Evaluation, Preclinical
Electrophysiology
Electrophysiology - methods
Ether-A-Go-Go Potassium Channels - chemistry
Ether-A-Go-Go Potassium Channels - genetics
Ether-A-Go-Go Potassium Channels - metabolism
Flavonoids
Fluorescence
Health screening
Indole
Indoles
Insects
Ion channels
Libraries
Ligands
Medical screening
Metabolites
Mice
Mutagenesis
Physiology
Physiology/Cell Signaling
Potassium
Protein Binding
Protein Structure, Tertiary
Proteins
Regulators
Smooth muscle
Tryptophan
Tryptophan - chemistry
Tryptophan - metabolism
Xenopus
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Ether-à-go-go (EAG) channels are expressed throughout the central nervous system and are also crucial regulators of cell cycle and tumor progression. The large intracellular amino- and carboxy- terminal domains of EAG1 each share similarity with known ligand binding motifs in other proteins, yet EAG1 channels have no known regulatory ligands. Here we screened a library of small biologically relevant molecules against EAG1 channels with a novel two-pronged screen to identify channel regulators. In one arm of the screen we used electrophysiology to assess the functional effects of the library compounds on full-length EAG1 channels. In an orthogonal arm, we used tryptophan fluorescence to screen for binding of the library compounds to the isolated C-terminal region. Several compounds from the flavonoid, indole and benzofuran chemical families emerged as binding partners and/or regulators of EAG1 channels. The two-prong screen can aid ligand and drug discovery for ligand-binding domains of other ion channels.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0012523