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PLoS One. 2010 Sep 2;5(9). pii: e12523. doi: 10.1371/journal.pone.0012523.

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

Author information

1
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington, United States of America.

Abstract

BACKGROUND:

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.

METHODOLOGY/PRINCIPAL FINDINGS:

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.

CONCLUSIONS/SIGNIFICANCE:

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.

PMID:
20824064
PMCID:
PMC2932742
DOI:
10.1371/journal.pone.0012523
[Indexed for MEDLINE]
Free PMC Article

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