View source for 1cnn


==OMEGA-CONOTOXIN MVIIC FROM CONUS MAGUS==
<StructureSection load='1cnn' size='340' side='right'caption='[[1cnn]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1cnn]] 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=1CNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CNN FirstGlance]. <br>
</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='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=1cnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cnn OCA], [https://pdbe.org/1cnn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cnn RCSB], [https://www.ebi.ac.uk/pdbsum/1cnn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cnn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O17C_CONMA O17C_CONMA] Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav). This toxin preferentially blocks P/Q-type calcium channels (Cav2.1/CACNA1A) (IC(50)=0.60 nM) (PubMed:1352986, PubMed:10938268). Shows also an inhibition on Cav2.2/CACNA1A channels (IC(50)=7.0 nM) (PubMed:10938268).<ref>PMID:10938268</ref> <ref>PMID:1352986</ref> 
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== Publication Abstract from PubMed ==
The omega-conotoxins are a set of structurally related, four-loop, six cysteine containing peptides, that have a range of selectivities for different subtypes of the voltage-sensitive calcium channel (VSCC). To investigate the basis of the selectivity displayed by these peptides, we have studied the binding affinities of two naturally occurring omega-conotoxins, MVIIA and MVIIC and a series of 14 MVIIA/MVIIC loop hybrids using radioligand binding assays for N and P/Q-type Ca2+channels in rat brain tissue. A selectivity profile was developed from the ratio of relative potencies at N-type VSCCs (using [125I]GVIA radioligand binding assays) and P/Q-type VSCCs (using [125I]MVIIC radioligand binding assays). In these peptides, loops 2 and 4 make the greatest contribution to VSCC subtype selectivity, while the effects of loops 1 and 3 are negligible. Peptides with homogenous combinations of loop 2 and 4 display clear selectivity preferences, while those with heterogeneous combinations of loops 2 and 4 are less discriminatory. 1H NMR spectroscopy revealed that the global folds of MVIIA, MVIIC and the 14 loop hybrid peptides were similar; however, several differences in local structure were identified. Based on the binding data and the 3D structures of MVIIA, GVIA and MVIIC, we have developed a preliminary pharmacophore based on the omega-conotoxin residues most likely to interact with the N-type VSCC.

Structure-activity relationships of omega-conotoxins MVIIA, MVIIC and 14 loop splice hybrids at N and P/Q-type calcium channels.,Nielsen KJ, Adams D, Thomas L, Bond T, Alewood PF, Craik DJ, Lewis RJ J Mol Biol. 1999 Jun 25;289(5):1405-21. PMID:10373375<ref>PMID:10373375</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 1cnn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Conus magus]]
[[Category: Large Structures]]
[[Category: Adams D]]
[[Category: Alewood PF]]
[[Category: Bond T]]
[[Category: Craik DJ]]
[[Category: Lewis RJ]]
[[Category: Nielsen KJ]]
[[Category: Thomas L]]