View source for 9nvh


==NMR structure of conotoxin k-SrXIA==
<StructureSection load='9nvh' size='340' side='right'caption='[[9nvh]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9nvh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_spurius Conus spurius]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9NVH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9NVH FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=9nvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9nvh OCA], [https://pdbe.org/9nvh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9nvh RCSB], [https://www.ebi.ac.uk/pdbsum/9nvh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9nvh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/I2BA_CONSP I2BA_CONSP] Kappa-conotoxins bind and inhibit voltage-gated potassium channels. This toxin inhibits Kv1.2/KCNA2 and Kv1.6/KCNA6. Produces stiffening of body, limbs and tail when injected intracranially into mice.<ref>PMID:17166627</ref> <ref>PMID:20403399</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The biologically active components of Conus venoms are mainly small peptides with disulfide-bonded structures. Some conotoxins contain post-translational modifications as an evolutionary strategy to enhance their potency and selectivity towards ion channels and receptors. Few conotoxins are known to target mammalian Kv1 channels. kappa-SrXIA from the venom of Conus spurius inhibits the voltage-gated potassium Kv1.2 and Kv1.6 channels through a basic ring of Arg. The 32 amino acid kappa-SrXIA has eight Cys residues arranged in the pattern that defines the I-superfamily with four disulfide bridges, two gamma-carboxy-glutamates (Gla), and a Pro-amidated C-terminus (X). In this study, we obtained and determined the biological activity and NMR structure of recombinant kappa-SrXIA without Gla and X. The conotoxin cDNA was expressed in E. coli CD41 and purified by GST-affinity chromatography and RP-HPLC. Pharmacological assays were performed by two-electrode voltage-clamp recordings in Xenopus laevis oocytes expressing recombinant Kv1.1, Kv1.2, Kv1.3, Kv1.4 and Kv1.6 channels. Except for Kv1.3, kappa-Sr-XIA irreversibly blocked Kv1 channels displaying a lower affinity and a slower inhibition kinetics than native conotoxin. Even when kappa-SrXIA displayed a high structural similarity to GXIA from the I(3)-superfamily, the resultant disulfide connectivity forming an ICK+1 motif showed two antiparallel beta-strands as iota-RXIA from the I(1)-superfamily. This study represents the first 3D NMR structure for a member of the I(2)-superfamily.

Block of Kv1 potassium channels and NMR structure of recombinant conotoxin kappa-SrXIA.,Escobar LI, Quezada Suaste CD, Salvador C, Aparicio DL, Melchor-Meneses CM, Bravo-Martinez J, de la Rosa V, Lopez-Gonzalez Z, Del Rio-Portilla F Toxicon. 2025 May 3;262:108384. doi: 10.1016/j.toxicon.2025.108384. PMID:40324600<ref>PMID:40324600</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9nvh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Conus spurius]]
[[Category: Large Structures]]
[[Category: Melchor-Meneses CM]]
[[Category: Del Rio-Portilla F]]