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| | ==NMR Solution Structures of delta-Conotoxin EVIA from Conus ermineus that Selectively Acts on Vertebrate Neuronal Na+ Channels, LEU12-PRO13 Cis isomer== | | ==NMR Solution Structures of delta-Conotoxin EVIA from Conus ermineus that Selectively Acts on Vertebrate Neuronal Na+ Channels, LEU12-PRO13 Cis isomer== |
| - | <StructureSection load='1g1z' size='340' side='right' caption='[[1g1z]], [[NMR_Ensembles_of_Models | 18 NMR models]]' scene=''> | + | <StructureSection load='1g1z' size='340' side='right'caption='[[1g1z]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1g1z]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G1Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1G1Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1g1z]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_ermineus Conus ermineus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G1Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1G1Z FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <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</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1g1p|1g1p]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1g1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g1z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1g1z RCSB], [http://www.ebi.ac.uk/pdbsum/1g1z PDBsum]</span></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=1g1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g1z OCA], [https://pdbe.org/1g1z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1g1z RCSB], [https://www.ebi.ac.uk/pdbsum/1g1z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1g1z ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CXD6A_CONER CXD6A_CONER]] Delta-conotoxins bind to site 6 of voltage-gated sodium channels and inhibit the inactivation process. This toxin inhibits sodium channel inactivation in neuronal membranes from amphibians and mammals (Nav1.2a/SCN1A, Nav1.3/SCN3A and Nav1.6/SCN8A) upon binding to receptor site 6. | + | [https://www.uniprot.org/uniprot/U6A_CONER U6A_CONER] Delta-conotoxins bind to site 6 of voltage-gated sodium channels and inhibit the inactivation process. This toxin inhibits sodium channel inactivation in neuronal membranes from amphibians and mammals (Nav1.2a/SCN1A, Nav1.3/SCN3A and Nav1.6/SCN8A) upon binding to receptor site 6.<ref>PMID:14615484</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 1g1z" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Gall, F Le]] | + | [[Category: Conus ermineus]] |
| - | [[Category: Lamthanh, H]] | + | [[Category: Large Structures]] |
| - | [[Category: Lancelin, J M]] | + | [[Category: Lamthanh H]] |
| - | [[Category: Menez, A]] | + | [[Category: Lancelin JM]] |
| - | [[Category: Volpon, L]] | + | [[Category: Le Gall F]] |
| - | [[Category: Cis/trans isomerism of leu12-pro13 peptide bond]] | + | [[Category: Menez A]] |
| - | [[Category: Hydroxyproline]] | + | [[Category: Volpon L]] |
| - | [[Category: Three disulfide linkage]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
U6A_CONER Delta-conotoxins bind to site 6 of voltage-gated sodium channels and inhibit the inactivation process. This toxin inhibits sodium channel inactivation in neuronal membranes from amphibians and mammals (Nav1.2a/SCN1A, Nav1.3/SCN3A and Nav1.6/SCN8A) upon binding to receptor site 6.[1]
Publication Abstract from PubMed
Delta-conotoxin EVIA, from Conus ermineus, is a 32-residue polypeptide cross-linked by three disulfide bonds forming a four-loop framework. delta-Conotoxin EVIA is the first conotoxin known to inhibit sodium channel inactivation in neuronal membranes from amphibians and mammals (subtypes rNa(v)1.2a, rNa(v)1.3, and rNa(v)1.6), without affecting rat skeletal muscle (subtype rNa(v)1.4) and human cardiac muscle (subtype hNa(v)1.5) sodium channel (Barbier, J., Lamthanh, H., Le Gall, F., Favreau, P., Benoit, E., Chen, H., Gilles, N., Ilan, N., Heinemann, S. F., Gordon, D., Menez, A., and Molgo, J. (2004) J. Biol. Chem. 279, 4680-4685). Its structure was solved by NMR and is characterized by a 1:1 cis/trans isomerism of the Leu(12)-Pro(13) peptide bond in slow exchange on the NMR time scale. The structure of both cis and trans isomers could be calculated separately. The isomerism occurs within a specific long disordered loop 2, including residues 11-19. These contribute to an important hydrophobic patch on the surface of the toxin. The rest of the structure matches the "inhibitor cystine-knot motif" of conotoxins from the "O superfamily" with a high structural order. To probe a possible functional role of the Leu(12)-Pro(13) cis/trans isomerism, a Pro(13) --> Ala delta-conotoxin EVIA was synthesized and shown to exist only as a trans isomer. P13A delta-conotoxin EVIA was estimated only two times less active than the wild-type EVIA in binding competition to rat brain synaptosomes and when injected intracerebroventricularly into mice.
NMR solution structures of delta-conotoxin EVIA from Conus ermineus that selectively acts on vertebrate neuronal Na+ channels.,Volpon L, Lamthanh H, Barbier J, Gilles N, Molgo J, Menez A, Lancelin JM J Biol Chem. 2004 May 14;279(20):21356-66. Epub 2004 Feb 19. PMID:14976206[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Barbier J, Lamthanh H, Le Gall F, Favreau P, Benoit E, Chen H, Gilles N, Ilan N, Heinemann SH, Gordon D, Ménez A, Molgó J. A delta-conotoxin from Conus ermineus venom inhibits inactivation in vertebrate neuronal Na+ channels but not in skeletal and cardiac muscles. J Biol Chem. 2004 Feb 6;279(6):4680-5. PMID:14615484 doi:10.1074/jbc.M309576200
- ↑ Volpon L, Lamthanh H, Barbier J, Gilles N, Molgo J, Menez A, Lancelin JM. NMR solution structures of delta-conotoxin EVIA from Conus ermineus that selectively acts on vertebrate neuronal Na+ channels. J Biol Chem. 2004 May 14;279(20):21356-66. Epub 2004 Feb 19. PMID:14976206 doi:http://dx.doi.org/10.1074/jbc.M309594200
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