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| | ==ALPHA-CONOTOXIN IMI== | | ==ALPHA-CONOTOXIN IMI== |
| - | <StructureSection load='1cnl' size='340' side='right'caption='[[1cnl]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='1cnl' size='340' side='right'caption='[[1cnl]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1cnl]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CNL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CNL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1cnl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_imperialis Conus imperialis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CNL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CNL FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 10 models</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=1cnl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cnl OCA], [http://pdbe.org/1cnl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1cnl RCSB], [http://www.ebi.ac.uk/pdbsum/1cnl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1cnl ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1cnl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cnl OCA], [https://pdbe.org/1cnl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cnl RCSB], [https://www.ebi.ac.uk/pdbsum/1cnl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cnl ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CA1_CONIM 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.<ref>PMID:8206995</ref> | + | [https://www.uniprot.org/uniprot/CA1_CONIM 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.<ref>PMID:8206995</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Conus imperialis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Craik, D J]] | + | [[Category: Craik DJ]] |
| - | [[Category: Daly, N L]] | + | [[Category: Daly NL]] |
| - | [[Category: Gehrmann, J]] | + | [[Category: Gehrmann J]] |
| - | [[Category: Conotoxin]]
| + | |
| - | [[Category: Nicotinic acetylcholine receptor blocker]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
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
alpha-Conotoxin ImI derives from the venom of Conus imperialis and is the first and only small-peptide ligand that selectively binds to the neuronal alpha7 homopentameric subtype of the nicotinic acetylcholine receptor (nAChR). This receptor subtype is a possible drug target for several neurological disorders. The cysteines are connected in the pairs Cys2-Cys8 and Cys3-Cys12. To date it is the only alpha-conotoxin with a 4/3 residue spacing between the cysteines. The structure of ImI has been determined by 1H NMR spectroscopy in aqueous solution. The NMR structure is of high quality, with a backbone pairwise rmsd of 0.34 A for a family of 19 structures, and comprises primarily a series of nested beta turns. Addition of organic solvent does not perturb the solution structure. The first eight residues of ImI are identical to the larger, but related, conotoxin EpI and adopt a similar structure, despite a truncated second loop. Residues important for binding of ImI to the alpha7 nAChR are all clustered on one face of the molecule. Once further binding data for EpI and ImI are available, the ImI structure will allow for design of novel alpha7 nAChR-specific agonists and antagonists with a wide range of potential pharmaceutical applications.
Solution structure of alpha-conotoxin ImI by 1H nuclear magnetic resonance.,Gehrmann J, Daly NL, Alewood PF, Craik DJ J Med Chem. 1999 Jul 1;42(13):2364-72. PMID:10395477[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
- ↑ Gehrmann J, Daly NL, Alewood PF, Craik DJ. Solution structure of alpha-conotoxin ImI by 1H nuclear magnetic resonance. J Med Chem. 1999 Jul 1;42(13):2364-72. PMID:10395477 doi:http://dx.doi.org/10.1021/jm990114p
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