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==NMR solution structure of leech peptide HSTX-I==
<StructureSection load='6wqr' size='340' side='right'caption='[[6wqr]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WQR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WQR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 21 models</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=6wqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wqr OCA], [https://pdbe.org/6wqr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wqr RCSB], [https://www.ebi.ac.uk/pdbsum/6wqr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wqr ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The role of voltage-gated sodium (NaV) channels in pain perception is indisputable. Of particular interest as targets for the development of pain therapeutics are the tetrodotoxin-resistant isoforms NaV1.8 and NaV1.9, based on animal as well as human genetic studies linking these ion channel subtypes to the pathogenesis of pain. However, only a limited number of inhibitors selectively targeting these channels have been reported. HSTX-I is a peptide toxin identified from saliva of the leech Haemadipsa sylvestris. The native 23-residue peptide, stabilised by two disulfide bonds, has been reported to inhibit rat NaV1.8 and mouse NaV1.9 with low micromolar activity, and may therefore represent a scaffold for development of novel modulators with activity at human tetrodotoxin-resistant NaV isoforms. We synthetically produced this hydrophobic peptide in high yield using a one-pot oxidation and single step purification and determined the three-dimensional solution structure of HSTX-I using NMR solution spectroscopy. However, in our hands, the synthetic HSTX-I displayed only very modest activity at human NaV1.8 and NaV1.9, and lacked analgesic efficacy in a murine model of inflammatory pain.

Pharmacological activity and NMR solution structure of the leech peptide HSTX-I.,McMahon KL, Tay B, Deuis JR, Tanaka BS, Peigneur S, Jin AH, Tytgat J, Waxman SG, Dib-Hajj SD, Vetter I, Schroeder CI Biochem Pharmacol. 2020 Jun 7:114082. doi: 10.1016/j.bcp.2020.114082. PMID:32524995<ref>PMID:32524995</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: McMahon KL]]
[[Category: Schroeder CI]]