Structure-activity relationships of alpha-conotoxins targeting neuronal nicotinic acetylcholine receptors.
alpha-Conotoxins that target the neuronal nicotinic acetylcholine receptor have a range of potential therapeutic applications and are valuable probes for examining receptor subtype selectivity. The three-dimensional structures of about half of the known neuronal specific alpha-conotoxins have now been determined and have a consensus fold containing a helical region braced by two conserved disulfide bonds. These disulfide bonds define the two-loop framework characteristic for alpha-conotoxins, CCX(m)CX(n)C, where loop 1 comprises four residues (m = 4) and loop 2 between three and seven residues (n = 3, 6 or 7). Structural studies, particularly using NMR spectroscopy have provided an insight into the role and spatial location of residues implicated in receptor binding and biological activity.
Millard
Emma L
EL
Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Daly
Norelle L
NL
Craik
David J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004220:Disulfides / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D011487:Protein Conformation; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D020916:Conotoxins; D004220:Disulfides; D011978:Receptors, Nicotinic