|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==NMR STRUCTURE OF OMEGA-CONOTOXIN MVIIA: CONSTRAINTS ON DISULPHIDE BRIDGES== | | ==NMR STRUCTURE OF OMEGA-CONOTOXIN MVIIA: CONSTRAINTS ON DISULPHIDE BRIDGES== |
| - | <StructureSection load='1dw4' size='340' side='right'caption='[[1dw4]], [[NMR_Ensembles_of_Models | 32 NMR models]]' scene=''> | + | <StructureSection load='1dw4' size='340' side='right'caption='[[1dw4]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1dw4]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DW4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DW4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1dw4]] 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=1DW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DW4 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, 32 models</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dw5|1dw5]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dw4 OCA], [http://pdbe.org/1dw4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1dw4 RCSB], [http://www.ebi.ac.uk/pdbsum/1dw4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1dw4 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=1dw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dw4 OCA], [https://pdbe.org/1dw4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dw4 RCSB], [https://www.ebi.ac.uk/pdbsum/1dw4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dw4 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:26344359, PubMed:34589389, PubMed:7826361). 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 == |
| Line 23: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Conus magus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Atkinson, R A]] | + | [[Category: Atkinson RA]] |
| - | [[Category: Dejaegere, A]] | + | [[Category: Dejaegere A]] |
| - | [[Category: Kieffer, B]] | + | [[Category: Kieffer B]] |
| - | [[Category: Lefevre, J F]] | + | [[Category: Lefevre J-F]] |
| - | [[Category: Sirockin, F]] | + | [[Category: Sirockin F]] |
| - | [[Category: Calcium channel]]
| + | |
| - | [[Category: Conformational exchange]]
| + | |
| - | [[Category: Conotoxin]]
| + | |
| - | [[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:26344359, PubMed:34589389, PubMed:7826361). 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
omega-Conotoxin MVIIA is a 25-residue, disulfide-bridged polypeptide from the venom of the sea snail Conus magus that binds to neuronal N-type calcium channels. It forms a compact folded structure, presenting a loop between Cys8 and Cys15 that contains a set of residues critical for its binding. The loop does not have a unique defined structure, nor is it intrinsically flexible. Broadening of a subset of resonances in the NMR spectrum at low temperature, anomalous temperature dependence of the chemical shifts of some resonances, and exchange contributions to J(0) from (13)C relaxation measurements reveal that conformational exchange affects the residues in this loop. The effects of this exchange on the calculated structure of omega-conotoxin MVIIA are discussed. The exchange appears to be associated with a change in the conformation of the disulfide bridge Cys8-Cys20. The implications for the use of the omega-conotoxins as a scaffold for carrying other functions is discussed.
Structural and dynamic characterization of omega-conotoxin MVIIA: the binding loop exhibits slow conformational exchange.,Atkinson RA, Kieffer B, Dejaegere A, Sirockin F, Lefevre JF Biochemistry. 2000 Apr 11;39(14):3908-19. PMID:10747778[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
- ↑ Atkinson RA, Kieffer B, Dejaegere A, Sirockin F, Lefevre JF. Structural and dynamic characterization of omega-conotoxin MVIIA: the binding loop exhibits slow conformational exchange. Biochemistry. 2000 Apr 11;39(14):3908-19. PMID:10747778
|
