This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

1mvi

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

N-TYPE CALCIUM CHANNEL BLOCKER, OMEGA-CONOTOXIN MVIIA, NMR, 15 STRUCTURES

Structural highlights

1mvi is a 1 chain structure with sequence from Conus magus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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^[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
↑ Nielsen KJ, Thomas L, Lewis RJ, Alewood PF, Craik DJ. A consensus structure for omega-conotoxins with different selectivities for voltage-sensitive calcium channel subtypes: comparison of MVIIA, SVIB and SNX-202. J Mol Biol. 1996 Oct 25;263(2):297-310. PMID:8913308 doi:S0022-2836(96)90576-8

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1mvi"

@@ Line 1: / Line 1: @@
 ==N-TYPE CALCIUM CHANNEL BLOCKER, OMEGA-CONOTOXIN MVIIA, NMR, 15 STRUCTURES==
-<StructureSection load='1mvi' size='340' side='right'caption='[[1mvi]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''>
+<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/Conma Conma]. 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>
+<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='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='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/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;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Conma]]
+[[Category: Conus magus]]
 [[Category: Large Structures]]
-[[Category: Alewood, P F]]
+[[Category: Alewood PF]]
-[[Category: Craik, D J]]
+[[Category: Craik DJ]]
-[[Category: Lewis, R J]]
+[[Category: Lewis RJ]]
-[[Category: Nielsen, K J]]
+[[Category: Nielsen KJ]]
-[[Category: Thomas, L]]
+[[Category: Thomas L]]
-[[Category: Conus magus peptide specific to n-type voltage sensitive calcium channel]]
-[[Category: Neurotoxin]]

1mvi

From Proteopedia

Current revision

N-TYPE CALCIUM CHANNEL BLOCKER, OMEGA-CONOTOXIN MVIIA, NMR, 15 STRUCTURES

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox