The three-dimensional structure of the analgesic alpha-conotoxin, RgIA.
The alpha-conotoxin RgIA is a selective antagonist of the alpha9alpha10 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 alpha9alpha10 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.
Clark
Richard J
RJ
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Daly
Norelle L
NL
Halai
Reena
R
Nevin
Simon T
ST
Adams
David J
DJ
Craik
David J
DJ
D000595:Amino Acid Sequence; D000700:Analgesics / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D020916:Conotoxins / Q000737:chemistry* / Q000378:metabolism; D052078:Conus Snail / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D017510:Protein Folding
D000700:Analgesics; D020916:Conotoxins; C510079:conotoxin alpha-RgIA, Conus regius