alpha-Conotoxin OmIA from Conus omaria is the only alpha-conotoxin that shows a similar to 20-fold higher affinity to the alpha 3 beta 2 over the alpha 6 beta 2 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 alpha 4/7 subfamily conotoxins. Reduced size of the hydrophilic area in alpha-conotoxin OmIA seems to be associated with the reduced affinity towards the alpha 6 beta 2 nAChR subtype. (c) 2006 Elsevier Inc. All rights reserved.