The three-dimensional structure of the analgesic α-conotoxin, RgIA

The alpha-conotoxin RgIA is a selective antagonist of the alpha 9 alpha 10 nicotinic acetylcholine receptor and has been shown to be a potent analgesic and reduces nerve injury associated inflammation. RgIA was chemically synthesized and found to fold into two disulfide isomers, globular and ribbon. The native globular isomer inhibited ACh-evoked currents reversibly in oocytes expressing rat alpha 9 alpha 10 nAChRs but the ribbon isomer was inactive. We determined the three-dimensional structure of RgIA using NMR methods to assist in elucidating the molecular role of RgIA in analgesia and inflammation. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.