Structural highlights
Function
[CA1A_CONOM] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks alpha-3/beta-2 (IC(50)=11 nM), alpha-7 (IC(50)=27.1) and alpha-6/alpha-3-beta-2-beta-3 (IC(50)=201 nM) subunits of nAChR.[1]
Publication Abstract from PubMed
alpha-Conotoxin OmIA from Conus omaria is the only alpha-conotoxin that shows a approximately 20-fold higher affinity to the alpha3beta2 over the alpha6beta2 subtype of nicotinic acetylcholine receptor. We have determined a three-dimensional structure of alpha-conotoxin OmIA by nuclear magnetic resonance spectroscopy. alpha-Conotoxin OmIA has an "omega-shaped" overall topology with His(5)-Asn(12) forming an alpha-helix. Structural features of alpha-conotoxin OmIA responsible for its selectivity are suggested by comparing its surface characteristics with other functionally related alpha4/7 subfamily conotoxins. Reduced size of the hydrophilic area in alpha-conotoxin OmIA seems to be associated with the reduced affinity towards the alpha6beta2 nAChR subtype.
Solution conformation of a neuronal nicotinic acetylcholine receptor antagonist alpha-conotoxin OmIA that discriminates alpha3 vs. alpha6 nAChR subtypes.,Chi SW, Kim DH, Olivera BM, McIntosh JM, Han KH Biochem Biophys Res Commun. 2006 Jun 23;345(1):248-54. Epub 2006 Apr 27. PMID:16678128[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Talley TT, Olivera BM, Han KH, Christensen SB, Dowell C, Tsigelny I, Ho KY, Taylor P, McIntosh JM. Alpha-conotoxin OmIA is a potent ligand for the acetylcholine-binding protein as well as alpha3beta2 and alpha7 nicotinic acetylcholine receptors. J Biol Chem. 2006 Aug 25;281(34):24678-86. doi: 10.1074/jbc.M602969200. Epub 2006, Jun 27. PMID:16803900 doi:http://dx.doi.org/10.1074/jbc.M602969200
- ↑ Chi SW, Kim DH, Olivera BM, McIntosh JM, Han KH. Solution conformation of a neuronal nicotinic acetylcholine receptor antagonist alpha-conotoxin OmIA that discriminates alpha3 vs. alpha6 nAChR subtypes. Biochem Biophys Res Commun. 2006 Jun 23;345(1):248-54. Epub 2006 Apr 27. PMID:16678128 doi:http://dx.doi.org/S0006-291X(06)00889-8
