6wqr

From Proteopedia

(Difference between revisions)

Revision as of 11:06, 14 June 2023

NMR solution structure of leech peptide HSTX-I

Structural highlights

6wqr is a 1 chain structure with sequence from Haemadipsa sylvestris. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wang G, Long C, Liu W, Xu C, Zhang M, Li Q, Lu Q, Meng P, Li D, Rong M, Sun Z, Luo X, Lai R. Novel Sodium Channel Inhibitor From Leeches. Front Pharmacol. 2018 Mar 6;9:186. PMID:29559913 doi:10.3389/fphar.2018.00186
↑ 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
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6wqr"

Categories: Haemadipsa sylvestris | Large Structures | McMahon KL | Schroeder CI

@@ Line 1: / Line 1: @@
 ==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 ==
-<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'>[[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='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='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'>[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='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 ==
@@ Line 20: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Haemadipsa sylvestris]]
 [[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]]
-[[Category: Toxin]]

6wqr

From Proteopedia

Revision as of 11:06, 14 June 2023

NMR solution structure of leech peptide HSTX-I

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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