1pen | pdb_00001pen
ALPHA-CONOTOXIN PNI1
Structural highlights
Function[CA1A_CONPE] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4).[1] [2] Publication Abstract from PubMedBACKGROUND: alpha-Conotoxins are peptide toxins, isolated from Conus snails, that block the nicotinic acetylcholine receptor (nAChR). The 16-residue peptides PnIA and PnIB from Conus pennaceus incorporate the same disulfide framework as other alpha-conotoxins but differ in function from most alpha-conotoxins by blocking the neuronal nAChR, rather than the skeletal muscle subtype. The crystal structure determination of PnIA was undertaken to identify structural and surface features that might be important for biological activity. RESULTS: The 1.1 A crystal structure of synthetic PnIA was determined by direct methods using the Shake-and-Bake program. The three-dimensional structure incorporates a beta turn followed by two alpha-helical turns. The conformation is stabilised by two disulfide bridges that form the interior of the molecule, with all other side chains oriented outwards. CONCLUSIONS: The compact architecture of the PnIA toxin provides a rigid framework for presentation of chemical groups that are required for activity. The structure is characterized by distinct hydrophobic and polar surfaces; a 16 A separation of the sole positive and negative charges (these two charged residues being located at opposite ends of the molecule); a hydrophobic region and a protruding tyrosine side chain. These features may be important for the specific interaction of PnIA with neuronal nAChR. The 1.1 A crystal structure of the neuronal acetylcholine receptor antagonist, alpha-conotoxin PnIA from Conus pennaceus.,Hu SH, Gehrmann J, Guddat LW, Alewood PF, Craik DJ, Martin JL Structure. 1996 Apr 15;4(4):417-23. PMID:8740364[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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