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2bc8

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Revision as of 13:22, 10 September 2015

[Sec2,3,8,12]-ImI

Structural highlights

2bc8 is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2bc7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[CA1_CONIM] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian neuronal nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4). Has no effect on nAChRs composed of alpha-2/beta-2, alpha-3/beta-2, alpha-4/beta-2, alpha-2/beta-4, alpha-3/beta-4, or alpha-4/beta-4 subunits. Acts voltage-independently. Is highly active against the neuromuscular receptor in frog.^[1]

Publication Abstract from PubMed

Disulfide bonds are important structural motifs that play an essential role in maintaining the conformational stability of many bioactive peptides. Of particular importance are the conotoxins, which selectively target a wide range of ion channels that are implicated in numerous disease states. Despite the enormous potential of conotoxins as therapeutics, their multiple disulfide bond frameworks are inherently unstable under reducing conditions. Reduction or scrambling by thiol-containing molecules such as glutathione or serum albumin in intracellular or extracellular environments such as blood plasma can decrease their effectiveness as drugs. To address this issue, we describe a new class of selenoconotoxins where cysteine residues are replaced by selenocysteine to form isosteric and nonreducible diselenide bonds. Three isoforms of alpha-conotoxin ImI were synthesized by t-butoxycarbonyl chemistry with systematic replacement of one ([Sec(2,8)]ImI or [Sec(3,12)]ImI), or both ([Sec(2,3,8,12)]ImI) disulfide bonds with a diselenide bond. Each analogue demonstrated remarkable stability to reduction or scrambling under a range of chemical and biological reducing conditions. Three-dimensional structural characterization by NMR and CD spectroscopy indicates conformational preferences that are very similar to those of native ImI, suggesting fully isomorphic structures. Additionally, full bioactivity was retained at the alpha7 nicotinic acetylcholine receptor, with each selenoanalogue exhibiting a dose-response curve that overlaps with wild-type ImI, thus further supporting an isomorphic structure. These results demonstrate that selenoconotoxins can be used as highly stable scaffolds for the design of new drugs.

Alpha-selenoconotoxins, a new class of potent alpha7 neuronal nicotinic receptor antagonists.,Armishaw CJ, Daly NL, Nevin ST, Adams DJ, Craik DJ, Alewood PF J Biol Chem. 2006 May 19;281(20):14136-43. Epub 2006 Feb 24. PMID:16500898^[2]

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

References

↑ McIntosh JM, Yoshikami D, Mahe E, Nielsen DB, Rivier JE, Gray WR, Olivera BM. A nicotinic acetylcholine receptor ligand of unique specificity, alpha-conotoxin ImI. J Biol Chem. 1994 Jun 17;269(24):16733-9. PMID:8206995
↑ Armishaw CJ, Daly NL, Nevin ST, Adams DJ, Craik DJ, Alewood PF. Alpha-selenoconotoxins, a new class of potent alpha7 neuronal nicotinic receptor antagonists. J Biol Chem. 2006 May 19;281(20):14136-43. Epub 2006 Feb 24. PMID:16500898 doi:M512419200

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2bc8"

@@ Line 4: / Line 4: @@
 <table><tr><td colspan='2'>[[2bc8]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BC8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BC8 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2bc7|2bc7]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bc8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bc8 RCSB], [http://www.ebi.ac.uk/pdbsum/2bc8 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bc8 OCA], [http://pdbe.org/2bc8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bc8 RCSB], [http://www.ebi.ac.uk/pdbsum/2bc8 PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2bc8" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2bc8

From Proteopedia

Revision as of 13:22, 10 September 2015

[Sec2,3,8,12]-ImI

Structural highlights

Function

Publication Abstract from PubMed

References

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