2ns3

Publication Abstract from PubMed

BACKGROUND: Alpha-conotoxins have exciting therapeutic potential based on their high selectivity and affinity for nicotinic acetylcholine receptors. The spacing between the cysteine residues in alpha-conotoxins is variable, leading to the classification of sub-families. BuIA is the only alpha-conotoxin containing a 4/4 cysteine spacing and thus it is of significant interest to examine the structure of this conotoxin. RESULTS: In the current study we show the native globular disulfide connectivity of BuIA displays multiple conformations in solution whereas the non-native ribbon isomer has a single well-defined conformation. Despite having multiple conformations in solution the globular form of BuIA displays activity at the nicotinic acetylcholine receptor, contrasting with the lack of activity of the structurally well-defined ribbon isomer. CONCLUSION: These findings are opposite to the general trends observed for alpha-conotoxins where the native isomers have well-defined structures and the ribbon isomers are generally disordered. This study thus highlights the influence of the disulfide connectivity of BuIA on the dynamics of the three-dimensional structure.

Structure of alpha-conotoxin BuIA: influences of disulfide connectivity on structural dynamics.,Jin AH, Brandstaetter H, Nevin ST, Tan CC, Clark RJ, Adams DJ, Alewood PF, Craik DJ, Daly NL BMC Struct Biol. 2007 Apr 20;7:28. PMID:17445276^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.