View source for 6mjd


==NMR Solution structure of GIIIC==
<StructureSection load='6mjd' size='340' side='right'caption='[[6mjd]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6mjd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_geographus Conus geographus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MJD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MJD FirstGlance]. <br>
</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=6mjd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mjd OCA], [https://pdbe.org/6mjd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mjd RCSB], [https://www.ebi.ac.uk/pdbsum/6mjd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mjd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CM3C_CONGE CM3C_CONGE] Mu-conotoxins block voltage-gated sodium channels (Nav). This toxin shows potent activity on Nav1.4/SCN4A (IC(50)=286 nM), and weak activity on mNav1.6/SCN8A.<ref>PMID:30360356</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
mu-Conotoxins are potent and highly specific peptide blockers of voltage-gated sodium channels. In this study, the solution structure of mu-conotoxin GIIIC was determined using 2D NMR spectroscopy and simulated annealing calculations. Despite high sequence similarity, GIIIC adopts a three-dimensional structure that differs from the previously observed conformation of mu-conotoxins GIIIA and GIIIB due to the presence of a bulky, non-polar leucine residue at position 18. The side chain of L18 is oriented towards the core of the molecule and consequently the N-terminus is re-modeled and located closer to L18. The functional characterization of GIIIC defines it as a canonical mu-conotoxin that displays substantial selectivity towards skeletal muscle sodium channels (NaV), albeit with ~2.5-fold lower potency than GIIIA. GIIIC exhibited a lower potency of inhibition of NaV1.4 channels, but the same NaV selectivity profile when compared to GIIIA. These observations suggest that single amino acid differences that significantly affect the structure of the peptide do in fact alter its functional properties. Our work highlights the importance of structural factors, beyond the disulfide pattern and electrostatic interactions, in the understanding of the functional properties of bioactive peptides. The latter thus needs to be considered when designing analogues for further applications.

NMR Structure of mu-Conotoxin GIIIC: Leucine 18 Induces Local Repacking of the N-Terminus Resulting in Reduced NaV Channel Potency.,Harvey PJ, Kurniawan ND, Finol-Urdaneta RK, McArthur JR, Van Lysebetten D, Dash TS, Hill JM, Adams DJ, Durek T, Craik DJ Molecules. 2018 Oct 22;23(10). pii: molecules23102715. doi:, 10.3390/molecules23102715. PMID:30360356<ref>PMID:30360356</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6mjd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Conus geographus]]
[[Category: Large Structures]]
[[Category: Craik DJ]]
[[Category: Durek T]]
[[Category: Harvey PJ]]