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| | ==CONOTOXIN GS, NMR, 20 STRUCTURES== | | ==CONOTOXIN GS, NMR, 20 STRUCTURES== |
| - | <StructureSection load='1ag7' size='340' side='right' caption='[[1ag7]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1ag7' size='340' side='right'caption='[[1ag7]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1ag7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Conus_geographus Conus geographus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AG7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1AG7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1ag7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_geographus Conus geographus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AG7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AG7 FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CGU:GAMMA-CARBOXY-GLUTAMIC+ACID'>CGU</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ag7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ag7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ag7 RCSB], [http://www.ebi.ac.uk/pdbsum/1ag7 PDBsum]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CGU:GAMMA-CARBOXY-GLUTAMIC+ACID'>CGU</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene></td></tr> |
| - | <table> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ag7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ag7 OCA], [https://pdbe.org/1ag7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ag7 RCSB], [https://www.ebi.ac.uk/pdbsum/1ag7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ag7 ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/U6GS_CONGE U6GS_CONGE] Mu-conotoxins block voltage-gated sodium channels (Nav). No effect was observed upon injections into mice and goldfish (25 ug).<ref>PMID:2851318</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 1ag7" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Conus geographus]] | | [[Category: Conus geographus]] |
| - | [[Category: Alewood, P F.]] | + | [[Category: Large Structures]] |
| - | [[Category: Craik, D J.]] | + | [[Category: Alewood PF]] |
| - | [[Category: Hill, J M.]] | + | [[Category: Craik DJ]] |
| - | [[Category: Cystine knot motif]] | + | [[Category: Hill JM]] |
| - | [[Category: Mu-conotoxin]]
| + | |
| - | [[Category: Neurotoxin]]
| + | |
| - | [[Category: Sodium channel blocker]]
| + | |
| Structural highlights
Function
U6GS_CONGE Mu-conotoxins block voltage-gated sodium channels (Nav). No effect was observed upon injections into mice and goldfish (25 ug).[1]
Publication Abstract from PubMed
BACKGROUND: The venoms of Conus snails contain small, disulfide-rich inhibitors of voltage-dependent sodium channels. Conotoxin GS is a 34-residue polypeptide isolated from Conus geographus that interacts with the extracellular entrance of skeletal muscle sodium channels to prevent sodium ion conduction. Although conotoxin GS binds competitively with mu conotoxin GIIIA to the sodium channel surface, the two toxin types have little sequence identity with one another, and conotoxin GS has a four-loop structural framework rather than the characteristic three-loop mu-conotoxin framework. The structural study of conotoxin GS will form the basis for establishing a structure-activity relationship and understanding its interaction with the pore region of sodium channels. RESULTS: The three-dimensional structure of conotoxin GS was determined using two-dimensional NMR spectroscopy. The protein exhibits a compact fold incorporating a beta hairpin and several turns. An unusual feature of conotoxin GS is the exceptionally high proportion (100%) of cis-imide bond geometry for the three proline or hydroxyproline residues. The structure of conotoxin GS bears little resemblance to the three-loop mu conotoxins, consistent with the low sequence identity between the two toxin types and their different structural framework. However, the tertiary structure and cystine-knot motif formed by the three disulfide bonds is similar to that present in several other polypeptide ion channel inhibitors. CONCLUSIONS: This is the first three-dimensional structure of a 'four-loop' sodium channel inhibitor, and it represents a valuable new structural probe for the pore region of voltage-dependent sodium channels. The distribution of amino acid sidechains in the structure creates several polar and charged patches, and comparison with the mu conotoxins provides a basis for determining the binding surface of the conotoxin GS polypeptide.
Solution structure of the sodium channel antagonist conotoxin GS: a new molecular caliper for probing sodium channel geometry.,Hill JM, Alewood PF, Craik DJ Structure. 1997 Apr 15;5(4):571-83. PMID:9115446[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yanagawa Y, Abe T, Satake M, Odani S, Suzuki J, Ishikawa K. A novel sodium channel inhibitor from Conus geographus: purification, structure, and pharmacological properties. Biochemistry. 1988 Aug 23;27(17):6256-62. PMID:2851318
- ↑ Hill JM, Alewood PF, Craik DJ. Solution structure of the sodium channel antagonist conotoxin GS: a new molecular caliper for probing sodium channel geometry. Structure. 1997 Apr 15;5(4):571-83. PMID:9115446
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