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| | ==Solution structure of omega-conotoxin MVIIA with C-terminal Gly== | | ==Solution structure of omega-conotoxin MVIIA with C-terminal Gly== |
| - | <StructureSection load='1feo' size='340' side='right'caption='[[1feo]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1feo' size='340' side='right'caption='[[1feo]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1feo]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FEO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FEO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1feo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_magus Conus magus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FEO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FEO FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1omg|1omg]], [[1mvi|1mvi]], [[1dw4|1dw4]]</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='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=1feo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1feo OCA], [http://pdbe.org/1feo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1feo RCSB], [http://www.ebi.ac.uk/pdbsum/1feo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1feo ProSAT]</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=1feo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1feo OCA], [https://pdbe.org/1feo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1feo RCSB], [https://www.ebi.ac.uk/pdbsum/1feo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1feo ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CO17A_CONMA CO17A_CONMA]] Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels. This toxin blocks N-type calcium channels (Cav2.2/CACNA1B). | + | [https://www.uniprot.org/uniprot/O17A_CONMA O17A_CONMA] Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels. This toxin blocks Cav2.2/CACNA1B calcium channels (IC(50)=0.67-208 nM) (PubMed:7826361, PubMed:26344359, PubMed:34589389). It acts by neutralizing the outer electronegativity and sterically hindering the ion access path to the entrance of the channel selectivity filter (PubMed:34234349). It also shows antiproliferative effects on different glioma cell lines (M059J, U-138MG and U-251MG) (PubMed:28202361). In vivo, is lethal to fish (PubMed:26344359, PubMed:34589389). In vivo, injection into mammals induces adverse effects, such as tremor, diminution of spontaneous locomotor activity and bad coordinated locomotion (PubMed:26344359). In addition, it causes reduction of tumor area in the mouse glioma model, that is induced by the orthotopic injection of GL261 cells into the brain (PubMed:28202361).<ref>PMID:26344359</ref> <ref>PMID:34234349</ref> <ref>PMID:7826361</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 magus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gilbert, D E]] | + | [[Category: Gilbert DE]] |
| - | [[Category: Goldenberg, D P]] | + | [[Category: Goldenberg DP]] |
| - | [[Category: Koehn, R E]] | + | [[Category: Koehn RE]] |
| - | [[Category: Wagner, G]] | + | [[Category: Wagner G]] |
| - | [[Category: Beta sheet]]
| + | |
| - | [[Category: Disulfide knot]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
O17A_CONMA Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels. This toxin blocks Cav2.2/CACNA1B calcium channels (IC(50)=0.67-208 nM) (PubMed:7826361, PubMed:26344359, PubMed:34589389). It acts by neutralizing the outer electronegativity and sterically hindering the ion access path to the entrance of the channel selectivity filter (PubMed:34234349). It also shows antiproliferative effects on different glioma cell lines (M059J, U-138MG and U-251MG) (PubMed:28202361). In vivo, is lethal to fish (PubMed:26344359, PubMed:34589389). In vivo, injection into mammals induces adverse effects, such as tremor, diminution of spontaneous locomotor activity and bad coordinated locomotion (PubMed:26344359). In addition, it causes reduction of tumor area in the mouse glioma model, that is induced by the orthotopic injection of GL261 cells into the brain (PubMed:28202361).[1] [2] [3]
Publication Abstract from PubMed
Nuclear magnetic resonance spectroscopy was used to characterize the solution structure and backbone dynamics of a putative precursor form of omega-conotoxin MVIIA, a 25-amino-acid residue peptide antagonist of voltage-gated Ca(2+) channels. The mature peptide is found in the venom of a fish-hunting marine snail Conus magus and contains an amidated carboxyl terminus that is generated by oxidative cleavage of a Gly residue. The form examined in this study is identical to the mature peptide except for the presence of the unmodified carboxy-terminal Gly. This form, referred to as omega-MVIIA-Gly, has previously been shown to refold and form its disulfides more efficiently than the mature form, suggesting that the presence of the terminal Gly may favor folding in vivo. The nuclear magnetic resonance (NMR) structure determination indicated that the fold of omega-MVIIA-Gly is very similar to that previously determined for the mature form, but revealed that the terminal Gly residue participates in a network of hydrogen bonds involving both backbone and side chain atoms, very likely accounting for the enhanced stability and folding efficiency. (15)N relaxation experiments indicated that the backbone is well ordered on the nanosecond time scale but that residues 9-15 undergo a conformational exchange processes with a time constant of approximately 35 microseconds. Other studies have implicated this segment in the binding of the peptide to its physiological target, and the observed motions may play a role in allowing the peptide to enter the binding site
Solution structure and backbone dynamics of an omega-conotoxin precursor.,Goldenberg DP, Koehn RE, Gilbert DE, Wagner G Protein Sci. 2001 Mar;10(3):538-50. PMID:11344322[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang F, Yan Z, Liu Z, Wang S, Wu Q, Yu S, Ding J, Dai Q. Molecular basis of toxicity of N-type calcium channel inhibitor MVIIA. Neuropharmacology. 2016 Feb;101:137-45. PMID:26344359 doi:10.1016/j.neuropharm.2015.08.047
- ↑ Gao S, Yao X, Yan N. Structure of human Ca(v)2.2 channel blocked by the painkiller ziconotide. Nature. 2021 Aug;596(7870):143-147. PMID:34234349 doi:10.1038/s41586-021-03699-6
- ↑ Kim JI, Takahashi M, Ohtake A, Wakamiya A, Sato K. Tyr13 is essential for the activity of omega-conotoxin MVIIA and GVIA, specific N-type calcium channel blockers. Biochem Biophys Res Commun. 1995 Jan 17;206(2):449-54. PMID:7826361 doi:10.1006/bbrc.1995.1063
- ↑ Goldenberg DP, Koehn RE, Gilbert DE, Wagner G. Solution structure and backbone dynamics of an omega-conotoxin precursor. Protein Sci. 2001 Mar;10(3):538-50. PMID:11344322
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