View source for 1mvi


==N-TYPE CALCIUM CHANNEL BLOCKER, OMEGA-CONOTOXIN MVIIA, NMR, 15 STRUCTURES==
<StructureSection load='1mvi' size='340' side='right'caption='[[1mvi]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1mvi]] 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=1MVI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MVI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 15 models</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'>[https://proteopedia.org/fgij/fg.htm?mol=1mvi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mvi OCA], [https://pdbe.org/1mvi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mvi RCSB], [https://www.ebi.ac.uk/pdbsum/1mvi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mvi ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
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== Publication Abstract from PubMed ==
The omega-conotoxins are a set of structurally related peptides that have a wide range of specificities for different subtypes of the voltage-sensitive calcium channel (VSCC). To understand their VSCC subtype differentiation we studied the structure of two naturally occurring omega-conotoxins, MVIIA (specific to N-type) and SVIB (specific to P/Q-type) and a synthetic hybrid, SNX-202, which has altered specificities to both VSCC subtypes. The secondary structures of the three peptides are almost identical, consisting of a triple-stranded beta-sheet and several turns. A comparison of NMR data emphasizes the structural similarities between the peptides and highlights some minor structural differences. In the three-dimensional structures of SVIB and MVIIA these are manifested as orientational differences between two key loops. The structural rigidity of MVIIA was also examined. H alpha shifts are similar in a range of solvents, indicating that there are no solvent-induced changes in structure. The omega-conotoxins form a consensus structure despite differences in sequence and VSCC subtype specificity. This indicates that the omega-conotoxin macrosites for the N/P/Q-subfamily of VSCCs are related, with specificity for receptor targets being conferred by the positions of functional side-chains on the surface of the peptides.

A consensus structure for omega-conotoxins with different selectivities for voltage-sensitive calcium channel subtypes: comparison of MVIIA, SVIB and SNX-202.,Nielsen KJ, Thomas L, Lewis RJ, Alewood PF, Craik DJ J Mol Biol. 1996 Oct 25;263(2):297-310. PMID:8913308<ref>PMID:8913308</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1mvi" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Conus magus]]
[[Category: Large Structures]]
[[Category: Alewood PF]]
[[Category: Craik DJ]]
[[Category: Lewis RJ]]
[[Category: Nielsen KJ]]
[[Category: Thomas L]]