|
|
| (4 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==NMR solution structure of TRTX-Tp1a from the tarantula Thrixopelma pruriens== | | ==NMR solution structure of TRTX-Tp1a from the tarantula Thrixopelma pruriens== |
| - | <StructureSection load='2mxm' size='340' side='right' caption='[[2mxm]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mxm' size='340' side='right'caption='[[2mxm]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mxm]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MXM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MXM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mxm]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MXM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MXM FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2mxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mxm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2mxm RCSB], [http://www.ebi.ac.uk/pdbsum/2mxm PDBsum]</span></td></tr> | + | </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=2mxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mxm OCA], [https://pdbe.org/2mxm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mxm RCSB], [https://www.ebi.ac.uk/pdbsum/2mxm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mxm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/HPR3_THRPR HPR3_THRPR] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 13: |
Line 17: |
| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2mxm" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Rosengren, K]] | + | [[Category: Large Structures]] |
| - | [[Category: Cystine knot]] | + | [[Category: Rosengren K]] |
| - | [[Category: Sodium channel inhibitor]]
| + | |
| - | [[Category: Spider toxin]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
HPR3_THRPR
Publication Abstract from PubMed
Spider venoms are a rich source of ion channel modulators with therapeutic potential. Given the analgesic potential of subtype-selective inhibitors of voltage-gated sodium (NaV) channels, we screened spider venoms for inhibitors of human NaV1.7 using a high-throughput fluorescent assay. Here, we describe the discovery of a novel NaV1.7 inhibitor, mu-TRTX-Tp1a (Tp1a), isolated from the venom of the Peruvian green-velvet tarantula Thrixopelma pruriens. Recombinant and synthetic forms of this 33-residue peptide preferentially inhibited hNav1.7 > hNav1.6 > hNav1.2 > hNav1.1 > hNav1.3 channels in fluorescent assays. NaV1.7 inhibition was diminished (IC50 11.5 nM), and the association rate decreased, for the C-terminal acid form of Tp1a compared to the native amidated form (IC50 2.1 nM), suggesting that the peptide C-terminus contributes to its interaction with hNaV1.7. Tp1a had no effect on human voltage-gated calcium channels or nicotinic acetylcholine receptors at 5 muM. Unlike most spider toxins that modulate NaV channels, Tp1a inhibited hNav1.7 without significantly altering the voltage-dependence of activation or inactivation. Tp1a proved to be analgesic by reversing spontaneous pain induced in mice by intraplantar injection in OD1, a scorpion toxin that potentiates hNav1.7. The structure of Tp1a as determined using NMR spectroscopy revealed a classical inhibitor cystine knot motif (ICK). The molecular surface of Tp1a presents a hydrophobic patch surrounded by positively charged residues, with subtle differences to other ICK spider toxins that might contribute to its different pharmacological profile. Tp1a may help guide the development of more selective and potent hNaV1.7 inhibitors for treatment of chronic pain.
Identification and Characterization of ProTx-III [mu-TRTX-Tp1a], A New Voltage-Gated Sodium Channel Inhibitor from Venom of the Tarantula Thrixopelma Pruriens.,Cardoso FC, Dekan Z, Rosengren KJ, Erickson A, Vetter I, Deuis J, Herzig V, Alewood P, King GF, Lewis RJ Mol Pharmacol. 2015 May 15. pii: mol.115.098178. PMID:25979003[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cardoso FC, Dekan Z, Rosengren KJ, Erickson A, Vetter I, Deuis J, Herzig V, Alewood P, King GF, Lewis RJ. Identification and Characterization of ProTx-III [mu-TRTX-Tp1a], A New Voltage-Gated Sodium Channel Inhibitor from Venom of the Tarantula Thrixopelma Pruriens. Mol Pharmacol. 2015 May 15. pii: mol.115.098178. PMID:25979003 doi:http://dx.doi.org/10.1124/mol.115.098178
|
