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6wqr
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6wqr is ON HOLD Authors: Schroeder, C.I., McMahon, K.L. Description: NMR solution structure of leech peptide HSTX-I [[Category: Unreleased Structur...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==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'>[[6wqr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Haemadipsa_sylvestris Haemadipsa sylvestris]. 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='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> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/HSTX1_HAESL HSTX1_HAESL] Leech salivary gland peptide with unknown function (PubMed:32524995). It was originally described as exhibiting analgesic function by specifically inhibiting rodent Nav1.8/SCN10A and Nav1.9/SCN11A voltage-gated sodium channels, as well as showing analgesic activities in several mouse models (PubMed:29559913). In a second study, the synthetic peptide has been shown as having very weak activity on Nav1.8/SCN10A at the highest concentration tested (90 uM) and as being only very modestly active at hNav1.9/SCN11A, with a modest peak current size reduction (~19%) at high concentrations (10 uM) (PubMed:32524995). In addition, this second study reports no analgesic activity in a mouse model of inflammatory pain (PubMed:32524995).<ref>PMID:29559913</ref> <ref>PMID:32524995</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6wqr" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Haemadipsa sylvestris]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: McMahon KL]] | ||
| + | [[Category: Schroeder CI]] | ||
Current revision
NMR solution structure of leech peptide HSTX-I
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