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| ==Solution NMR structure of the omega conotoxin MoVIB from Conus moncuri== | | ==Solution NMR structure of the omega conotoxin MoVIB from Conus moncuri== |
- | <StructureSection load='6ceg' size='340' side='right' caption='[[6ceg]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='6ceg' size='340' side='right'caption='[[6ceg]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[6ceg]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CEG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CEG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ceg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus Conus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CEG 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></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=6ceg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ceg OCA], [http://pdbe.org/6ceg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ceg RCSB], [http://www.ebi.ac.uk/pdbsum/6ceg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ceg ProSAT]</span></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></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=6ceg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ceg OCA], [https://pdbe.org/6ceg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ceg RCSB], [https://www.ebi.ac.uk/pdbsum/6ceg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ceg ProSAT]</span></td></tr> |
| </table> | | </table> |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/O16A_CONMB O16A_CONMB] |
| <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: Rosengren, K J]] | + | [[Category: Conus]] |
- | [[Category: Ca2+ channel inhbitor]] | + | [[Category: Large Structures]] |
- | [[Category: Conotoxin]] | + | [[Category: Rosengren KJ]] |
- | [[Category: Omega-conotoxin]]
| + | |
- | [[Category: Toxin]]
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| Structural highlights
Function
O16A_CONMB
Publication Abstract from PubMed
Cone snails are a diverse group of predatory marine invertebrates that deploy remarkably complex venoms to rapidly paralyse worm, mollusc or fish prey. omega-Conotoxins are neurotoxic peptides from cone snail venoms that inhibit Cav2.2 voltage-gated calcium channel, demonstrating potential for pain management via intrathecal (IT) administration. Here, we isolated and characterized two novel omega-conotoxins, MoVIA and MoVIB from Conus moncuri, the first to be identified in vermivorous (worm-hunting) cone snails. MoVIA and MoVIB potently inhibited human Cav2.2 in fluorimetric assays and rat Cav2.2 in patch clamp studies, and both potently displaced radiolabeled omega-conotoxin GVIA ((125)I-GVIA) from human SH-SY5Y cells and fish brain membranes (IC50 2-9 pM). Intriguingly, an arginine at position 13 in MoVIA and MoVIB replaced the functionally critical tyrosine found in piscivorous omega-conotoxins. To investigate its role, we synthesized MoVIB-[R13Y] and MVIIA-[Y13R]. Interestingly, MVIIA-[Y13R] completely lost Cav2.2 activity and MoVIB-[R13Y] had reduced activity, indicating that Arg at position 13 was preferred in these vermivorous omega-conotoxins whereas tyrosine 13 is preferred in piscivorous omega-conotoxins. MoVIB reversed pain behavior in a rat neuropathic pain model, confirming that vermivorous cone snails are a new source of analgesic omega-conotoxins. Given vermivorous cone snails are ancestral to piscivorous species, our findings support the repurposing of defensive venom peptides in the evolution of piscivorous Conidae.
Novel analgesic omega-conotoxins from the vermivorous cone snail Conus moncuri provide new insights into the evolution of conopeptides.,Sousa SR, McArthur JR, Brust A, Bhola RF, Rosengren KJ, Ragnarsson L, Dutertre S, Alewood PF, Christie MJ, Adams DJ, Vetter I, Lewis RJ Sci Rep. 2018 Sep 7;8(1):13397. doi: 10.1038/s41598-018-31245-4. PMID:30194442[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sousa SR, McArthur JR, Brust A, Bhola RF, Rosengren KJ, Ragnarsson L, Dutertre S, Alewood PF, Christie MJ, Adams DJ, Vetter I, Lewis RJ. Novel analgesic omega-conotoxins from the vermivorous cone snail Conus moncuri provide new insights into the evolution of conopeptides. Sci Rep. 2018 Sep 7;8(1):13397. doi: 10.1038/s41598-018-31245-4. PMID:30194442 doi:http://dx.doi.org/10.1038/s41598-018-31245-4
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