A molecular mechanism for toxin block in N-type calcium channels.
A series of highly toxic snail venoms, the omega-conotoxins, have been shown to bind selectively, and often irreversibly to the N-type voltage-gated calcium channel alpha-1 subunit. The most potent of these is known as omega-conotoxin GVIA from the species Conus geographus, a marine snail that has been responsible for a number of human fatalities. Using theoretical techniques we present a plausible binding model of the conotoxin to a loop region of the channel. Our model of the toxin binding region also contains a possible EF-hand motif and we suggest that this Ca2+ binding domain lies on the ion permeation pathway, a possible Ca2+ recruitment site.
Doughty
S W
SW
Pharmaceutical Chemistry, School of Pharmacy, University of Bradford, West Yorkshire, UK.
Blaney
F E
FE
Orlek
B S
BS
Richards
W G
WG
D000595:Amino Acid Sequence; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D020866:omega-Conotoxin GVIA