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| | ==NMR solution structure of leech peptide HSTX-I== | | ==NMR solution structure of leech peptide HSTX-I== |
| - | <StructureSection load='6wqr' size='340' side='right'caption='[[6wqr]], [[NMR_Ensembles_of_Models | 21 NMR models]]' scene=''> | + | <StructureSection load='6wqr' size='340' side='right'caption='[[6wqr]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6wqr]] is a 1 chain structure. 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 [http://proteopedia.org/fgij/fg.htm?mol=6WQR FirstGlance]. <br> | + | <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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | </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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wqr OCA], [http://pdbe.org/6wqr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wqr RCSB], [http://www.ebi.ac.uk/pdbsum/6wqr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wqr ProSAT]</span></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> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: McMahon, K L]] | + | [[Category: McMahon KL]] |
| - | [[Category: Schroeder, C I]] | + | [[Category: Schroeder CI]] |
| - | [[Category: Antiparallel beta-sheet]]
| + | |
| - | [[Category: Disulfide-rich]]
| + | |
| - | [[Category: Hydrophobic]]
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| - | [[Category: Toxin]]
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| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ McMahon KL, Tay B, Deuis JR, Tanaka BS, Peigneur S, Jin AH, Tytgat J, Waxman SG, Dib-Hajj SD, Vetter I, Schroeder CI. Pharmacological activity and NMR solution structure of the leech peptide HSTX-I. Biochem Pharmacol. 2020 Jun 7:114082. doi: 10.1016/j.bcp.2020.114082. PMID:32524995 doi:http://dx.doi.org/10.1016/j.bcp.2020.114082
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