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| | ==MINIMAL CONFORMATION OF THE ALPHA-CONOTOXIN IMI FOR THE ALPHA7 NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR RECOGNITION== | | ==MINIMAL CONFORMATION OF THE ALPHA-CONOTOXIN IMI FOR THE ALPHA7 NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR RECOGNITION== |
| - | <StructureSection load='1g2g' size='340' side='right'caption='[[1g2g]], [[NMR_Ensembles_of_Models | 30 NMR models]]' scene=''> | + | <StructureSection load='1g2g' size='340' side='right'caption='[[1g2g]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1g2g]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G2G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1G2G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1g2g]] 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=1G2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1G2G 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, 30 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=1g2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g2g OCA], [http://pdbe.org/1g2g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1g2g RCSB], [http://www.ebi.ac.uk/pdbsum/1g2g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1g2g 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=1g2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g2g OCA], [https://pdbe.org/1g2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1g2g RCSB], [https://www.ebi.ac.uk/pdbsum/1g2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1g2g 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: Jegou-Matheron, C]] | + | [[Category: Jegou-Matheron C]] |
| - | [[Category: Lamthanh, H]] | + | [[Category: Lamthanh H]] |
| - | [[Category: Lancelin, J M]] | + | [[Category: Lancelin JM]] |
| - | [[Category: Menez, A]] | + | [[Category: Menez A]] |
| - | [[Category: Servent, D]] | + | [[Category: Servent D]] |
| - | [[Category: 3-10 helix]]
| + | |
| - | [[Category: Alpha-helix]]
| + | |
| - | [[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
The alpha-ImI conotoxin, a selective potent inhibitor of the mammalian neuronal alpha7 nicotinic acetylcholine receptor (n-AchR), was shown by point mutation or by L-alanine scanning to display two regions essential for bioactivity: the active site Asp5-Pro6-Arg7 in the first loop and Trp10 in the second loop. The deletion of the Cys3,Cys12 disulfide bond in the alpha-ImI scaffold, e.g. peptide II, had no effect on its binding affinity. CD spectra, NMR studies and structure calculations were carried out on the wild type alpha-ImI, the weakest analog (R7A) and peptide II (equipotent to alpha-ImI) in order to point out the conformational differences between these compounds. Then, an attempt to correlate the conformational data and the affinity results was proposed. CD and NMR data were identical for the R7A analog and alpha-ImI, revealing the crucial functional role of the Arg7 side chain. On the other hand, the scaffold of the first loop in peptide II was shown by NMR to represent the minimal conformation for the optimal interaction of the toxin with the neuronal alpha7 n-AchR. Last, the beta-turn forming property of the 6th residue (Pro) in the active site of the alpha-ImI can be correlated with its affinity.
Minimal conformation of the alpha-conotoxin ImI for the alpha7 neuronal nicotinic acetylcholine receptor recognition: correlated CD, NMR and binding studies.,Lamthanh H, Jegou-Matheron C, Servent D, Menez A, Lancelin JM FEBS Lett. 1999 Jul 9;454(3):293-8. PMID:10431825[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
- ↑ Lamthanh H, Jegou-Matheron C, Servent D, Menez A, Lancelin JM. Minimal conformation of the alpha-conotoxin ImI for the alpha7 neuronal nicotinic acetylcholine receptor recognition: correlated CD, NMR and binding studies. FEBS Lett. 1999 Jul 9;454(3):293-8. PMID:10431825
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