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| ==Solution Conformation of alpha-conotoxin PIA== | | ==Solution Conformation of alpha-conotoxin PIA== |
- | <StructureSection load='1zlc' size='340' side='right'caption='[[1zlc]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1zlc' size='340' side='right'caption='[[1zlc]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[1zlc]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZLC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZLC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1zlc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_purpurascens Conus purpurascens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZLC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZLC 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, 20 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=1zlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zlc OCA], [http://pdbe.org/1zlc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zlc RCSB], [http://www.ebi.ac.uk/pdbsum/1zlc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zlc 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=1zlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zlc OCA], [https://pdbe.org/1zlc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zlc RCSB], [https://www.ebi.ac.uk/pdbsum/1zlc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zlc ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/CA1A_CONPU CA1A_CONPU]] Alpha-conotoxins bind to the nicotinic acetylcholine receptors (nAChR) and inhibit them. This toxin blocks nAChR (alpha-6 or -3/beta-2 or -3 > alpha-3/beta-2 > alpha-3/beta-4). Does not block the muscle nor the major neuronal nAChR alpha-4/beta-2. Discriminates between nAChRs containing alpha-6 and alpha-3 subunits, being selective for alpha-6.<ref>PMID:13679412</ref> | + | [https://www.uniprot.org/uniprot/CA1A_CONPU CA1A_CONPU] Alpha-conotoxins bind to the nicotinic acetylcholine receptors (nAChR) and inhibit them. This toxin blocks nAChR (alpha-6 or -3/beta-2 or -3 > alpha-3/beta-2 > alpha-3/beta-4). Does not block the muscle nor the major neuronal nAChR alpha-4/beta-2. Discriminates between nAChRs containing alpha-6 and alpha-3 subunits, being selective for alpha-6.<ref>PMID:13679412</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 purpurascens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Chi, S W]] | + | [[Category: Chi S-W]] |
- | [[Category: Han, K H]] | + | [[Category: Han K-H]] |
- | [[Category: Kim, D H]] | + | [[Category: Kim D-H]] |
- | [[Category: Kim, J S]] | + | [[Category: Kim J-S]] |
- | [[Category: Lee, S H]] | + | [[Category: Lee S-H]] |
- | [[Category: McIntosh, J M]] | + | [[Category: McIntosh JM]] |
- | [[Category: Olivera, B M]] | + | [[Category: Olivera BM]] |
- | [[Category: Alpha-helix]]
| + | |
- | [[Category: Beta-turn]]
| + | |
- | [[Category: C-terminal amidation]]
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- | [[Category: Toxin]]
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- | [[Category: Two disulfide bond]]
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| Structural highlights
Function
CA1A_CONPU Alpha-conotoxins bind to the nicotinic acetylcholine receptors (nAChR) and inhibit them. This toxin blocks nAChR (alpha-6 or -3/beta-2 or -3 > alpha-3/beta-2 > alpha-3/beta-4). Does not block the muscle nor the major neuronal nAChR alpha-4/beta-2. Discriminates between nAChRs containing alpha-6 and alpha-3 subunits, being selective for alpha-6.[1]
Publication Abstract from PubMed
alpha-Conotoxin PIA is a novel nicotinic acetylcholine receptor (nAChR) antagonist isolated from Conus purpurascens that targets nAChR subtypes containing alpha6 and alpha3 subunits. alpha-conotoxin PIA displays 75-fold higher affinity for rat alpha6/alpha3beta2beta3 nAChRs than for rat alpha3beta2 nAChRs. We have determined the three-dimensional structure of alpha-conotoxin PIA by nuclear magnetic resonance spectroscopy. The alpha-conotoxin PIA has an "omega-shaped" overall topology as other alpha4/7 subfamily conotoxins. Yet, unlike other neuronally targeted alpha4/7-conotoxins, its N-terminal tail Arg1-Asp2-Pro3 protrudes out of its main molecular body because Asp2-Pro3-Cys4-Cys5 forms a stable type I beta-turn. In addition, a kink introduced by Pro15 in the second loop of this toxin provides a distinct steric and electrostatic environment from those in alpha-conotoxins MII and GIC. By comparing the structure of alpha-conotoxin PIA with other functionally related alpha-conotoxins we suggest structural features in alpha-conotoxin PIA that may be associated with its unique receptor recognition profile.
Solution structure of alpha-conotoxin PIA, a novel antagonist of alpha6 subunit containing nicotinic acetylcholine receptors.,Chi SW, Lee SH, Kim DH, Kim JS, Olivera BM, McIntosh JM, Han KH Biochem Biophys Res Commun. 2005 Dec 30;338(4):1990-7. Epub 2005 Nov 7. PMID:16289101[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dowell C, Olivera BM, Garrett JE, Staheli ST, Watkins M, Kuryatov A, Yoshikami D, Lindstrom JM, McIntosh JM. Alpha-conotoxin PIA is selective for alpha6 subunit-containing nicotinic acetylcholine receptors. J Neurosci. 2003 Sep 17;23(24):8445-52. PMID:13679412
- ↑ Chi SW, Lee SH, Kim DH, Kim JS, Olivera BM, McIntosh JM, Han KH. Solution structure of alpha-conotoxin PIA, a novel antagonist of alpha6 subunit containing nicotinic acetylcholine receptors. Biochem Biophys Res Commun. 2005 Dec 30;338(4):1990-7. Epub 2005 Nov 7. PMID:16289101 doi:http://dx.doi.org/S0006-291X(05)02460-5
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