title: Identification of a calcium channel modulator using a high throughput yeast two-hybrid screen.
abstract: The interaction of the N-type calcium channel beta3 subunit with the alpha1B subunit alters the activation/inactivation kinetics and the maximal conductance of the channel. The defined protein-protein interaction of the human alpha1B and beta3 subunits provides a target for small-molecule modulation of N-type channel activity. We describe a high throughput screen based on a counterselection yeast two-hybrid assay, which was used to identify small molecules that disrupt alpha1B-beta3 subunit interactions and inhibit N-type calcium channel activity. These small molecules may be a new class of calcium channel antagonists with therapeutic potential.
authors.affiliation: Wyeth-Ayerst Research, CNS Disorders, Princeton, NJ 08543, USA.
authors.forename: K
authors.initials: K
authors.lastname: Young
authors.forename: S
authors.initials: S
authors.lastname: Lin
authors.forename: L
authors.initials: L
authors.lastname: Sun
authors.forename: E
authors.initials: E
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Modi
authors.forename: S
authors.initials: S
authors.lastname: Hellings
authors.forename: M
authors.initials: M
authors.lastname: Husbands
authors.forename: B
authors.initials: B
authors.lastname: Ozenberger
authors.forename: R
authors.initials: R
authors.lastname: Franco
mesh_terms: D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000235:genetics; D018076:DNA, Complementary; D006801:Humans; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D020960:omega-Conotoxins
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018076:DNA, Complementary; D010455:Peptides; D020960:omega-Conotoxins; C078452:ziconotide; D009638:Norepinephrine