View source for 2cco


==STRUCTURE OF THE CALCIUM CHANNEL BLOCKER OMEGA CONOTOXIN GVIA, NMR, 20 STRUCTURES==
<StructureSection load='2cco' size='340' side='right'caption='[[2cco]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2cco]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_geographus Conus geographus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1cco 1cco]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CCO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CCO 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=HYP:4-HYDROXYPROLINE'>HYP</scene>, <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=2cco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cco OCA], [https://pdbe.org/2cco PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cco RCSB], [https://www.ebi.ac.uk/pdbsum/2cco PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cco ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O16A_CONGE O16A_CONGE] Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav). This toxin blocks N-type calcium channels (Cav2.2/CACNA1B) with a high potency (it displaces [125I]GVIA with an IC(50)=3.7-38 pM) (PubMed:10938268, PubMed:11724570).<ref>PMID:10938268</ref> <ref>PMID:11724570</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The polypeptide omega-conotoxin GVIA (GVIA) is an N-type calcium channel blocker from the venom of Conus geographus, a fish-hunting cone shell. Here we describe a high-resolution solution structure of this member of the 'inhibitor cystine knot' protein family. The structure, based on NMR data acquired at 600 MHz, has mean pairwise RMS differences of 0.25 +/- 0.06 and 1.07 +/- 0.14 A over the backbone heavy atoms and all heavy atoms, respectively. The solvent-accessible side chains are better defined than in previously published structures and provide an improved basis for docking GVIA with models of the calcium channel. Moreover, some side chain interactions important in GVIA folding in vitro and in stabilizing the native structure are defined clearly in the refined structure. Two qualitatively different backbone conformations in the segment from Thr11 to Asn14 persisted in the restrained simulated annealing calculations until a small number of lower bound constraints was included to prevent close contacts from occurring that did not correspond with peaks in the NOESY spectrum. It is possible that GVIA is genuinely flexible at this segment, spending a finite time in the alternative conformation, and this may influence its interaction with the calcium channel.

Refined solution structure of omega-conotoxin GVIA: implications for calcium channel binding.,Pallaghy PK, Norton RS J Pept Res. 1999 Mar;53(3):343-51. PMID:10231724<ref>PMID:10231724</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2cco" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Conus geographus]]
[[Category: Large Structures]]
[[Category: Norton RS]]
[[Category: Pallaghy PK]]