Identification of a calcium channel modulator using a high throughput yeast two-hybrid screen.
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.
Young
K
K
Wyeth-Ayerst Research, CNS Disorders, Princeton, NJ 08543, USA.
Lin
S
S
Sun
L
L
Lee
E
E
Modi
M
M
Hellings
S
S
Husbands
M
M
Ozenberger
B
B
Franco
R
R
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
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018076:DNA, Complementary; D010455:Peptides; D020960:omega-Conotoxins; C078452:ziconotide; D009638:Norepinephrine