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| - | [[Image:1axh.gif|left|200px]] | |
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| - | {{Structure
| + | ==ATRACOTOXIN-HVI FROM HADRONYCHE VERSUTA (AUSTRALIAN FUNNEL-WEB SPIDER, NMR, 20 STRUCTURES== |
| - | |PDB= 1axh |SIZE=350|CAPTION= <scene name='initialview01'>1axh</scene>
| + | <StructureSection load='1axh' size='340' side='right'caption='[[1axh]]' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND=
| + | <table><tr><td colspan='2'>[[1axh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Hadronyche_versuta Hadronyche versuta]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AXH FirstGlance]. <br> |
| - | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | |GENE=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1axh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1axh OCA], [https://pdbe.org/1axh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1axh RCSB], [https://www.ebi.ac.uk/pdbsum/1axh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1axh ProSAT]</span></td></tr> |
| - | }}
| + | </table> |
| - | | + | == Function == |
| - | '''ATRACOTOXIN-HVI FROM HADRONYCHE VERSUTA (AUSTRALIAN FUNNEL-WEB SPIDER, NMR, 20 STRUCTURES'''
| + | [https://www.uniprot.org/uniprot/TO1A_HADVE TO1A_HADVE] Reversibly and voltage-independently blocks both mid-low- (M-LVA) and high-voltage-activated (HVA) calcium channels in cockroach DUM neurons (PubMed:17610847). Is lethal to many insect species but not toxic to mammals (PubMed:9228949, PubMed:16779650). May target the insect high-voltage-activated calcium channel Dmca1D. Also inhibits acarines calcium channels. An extremely high toxin concentration partially inhibits Cav1.2/CACNA1C, Cav2.1/CACNA1A and Cav2.2/CACNA1B calcium channel of rats. As for omega-AcTx-Hv2a, the phenotypic effect of injection of this toxin into lone star ticks (Amblyomma americanum) is curling of all eight legs into closed loops.<ref>PMID:14608494</ref> <ref>PMID:15308644</ref> <ref>PMID:16330063</ref> <ref>PMID:17141372</ref> <ref>PMID:17610847</ref> <ref>PMID:9228949</ref> |
| - | | + | == Evolutionary Conservation == |
| - | | + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | ==Overview== | + | Check<jmol> |
| - | A family of potent insecticidal toxins has recently been isolated from the venom of Australian funnel web spiders. Among these is the 37-residue peptide omega-atracotoxin-HV1 (omega-ACTX-HV1) from Hadronyche versuta. We have chemically synthesized and folded omega-ACTX-HV1, shown that it is neurotoxic, ascertained its disulphide bonding pattern, and determined its three-dimensional solution structure using NMR spectroscopy. The structure consists of a solvent-accessible beta-hairpin protruding from a disulphide-bonded globular core comprising four beta-turns. The three intramolecular disulphide bonds from a cystine knot motif similar to that seen in several other neurotoxic peptides. Despite limited sequence identity, omega-ACTX-HV1 displays significant structural homology with the omega-agatoxins and omega-conotoxins, both of which are vertebrate calcium channel antagonists; however, in contrast with these toxins, we show that omega-ACTX-HV1 inhibits insect, but not mammalian, voltage-gated calcium channel currents.
| + | <jmolCheckbox> |
| - | | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ax/1axh_consurf.spt"</scriptWhenChecked> |
| - | ==About this Structure== | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | 1AXH is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Hadronyche_versuta Hadronyche versuta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AXH OCA].
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | | + | </jmolCheckbox> |
| - | ==Reference== | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1axh ConSurf]. |
| - | The structure of a novel insecticidal neurotoxin, omega-atracotoxin-HV1, from the venom of an Australian funnel web spider., Fletcher JI, Smith R, O'Donoghue SI, Nilges M, Connor M, Howden ME, Christie MJ, King GF, Nat Struct Biol. 1997 Jul;4(7):559-66. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9228949 9228949]
| + | <div style="clear:both"></div> |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Hadronyche versuta]] | | [[Category: Hadronyche versuta]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Donoghue, S I.O.]]
| + | [[Category: Fletcher JI]] |
| - | [[Category: Fletcher, J I.]] | + | [[Category: King GF]] |
| - | [[Category: King, G F.]] | + | [[Category: Nilges M]] |
| - | [[Category: Nilges, M.]] | + | [[Category: O'Donoghue SI]] |
| - | [[Category: cystine knot]] | + | |
| - | [[Category: funnel-web]]
| + | |
| - | [[Category: insecticidal toxin]]
| + | |
| - | [[Category: neurotoxin]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:03:28 2008''
| + | |
| Structural highlights
Function
TO1A_HADVE Reversibly and voltage-independently blocks both mid-low- (M-LVA) and high-voltage-activated (HVA) calcium channels in cockroach DUM neurons (PubMed:17610847). Is lethal to many insect species but not toxic to mammals (PubMed:9228949, PubMed:16779650). May target the insect high-voltage-activated calcium channel Dmca1D. Also inhibits acarines calcium channels. An extremely high toxin concentration partially inhibits Cav1.2/CACNA1C, Cav2.1/CACNA1A and Cav2.2/CACNA1B calcium channel of rats. As for omega-AcTx-Hv2a, the phenotypic effect of injection of this toxin into lone star ticks (Amblyomma americanum) is curling of all eight legs into closed loops.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Bloomquist JR. Mode of action of atracotoxin at central and peripheral synapses of insects. Invert Neurosci. 2003 Nov;5(1):45-50. Epub 2003 Nov 8. PMID:14608494 doi:http://dx.doi.org/10.1007/s10158-003-0027-z
- ↑ Tedford HW, Gilles N, Menez A, Doering CJ, Zamponi GW, King GF. Scanning mutagenesis of omega-atracotoxin-Hv1a reveals a spatially restricted epitope that confers selective activity against insect calcium channels. J Biol Chem. 2004 Oct 15;279(42):44133-40. Epub 2004 Aug 11. PMID:15308644 doi:http://dx.doi.org/10.1074/jbc.M404006200
- ↑ Mukherjee AK, Sollod BL, Wikel SK, King GF. Orally active acaricidal peptide toxins from spider venom. Toxicon. 2006 Feb;47(2):182-7. Epub 2005 Dec 5. PMID:16330063 doi:http://dx.doi.org/10.1016/j.toxicon.2005.10.011
- ↑ Tedford HW, Maggio F, Reenan RA, King G. A model genetic system for testing the in vivo function of peptide toxins. Peptides. 2007 Jan;28(1):51-6. Epub 2006 Dec 1. PMID:17141372 doi:http://dx.doi.org/10.1016/j.peptides.2006.08.026
- ↑ Chong Y, Hayes JL, Sollod B, Wen S, Wilson DT, Hains PG, Hodgson WC, Broady KW, King GF, Nicholson GM. The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium channels. Biochem Pharmacol. 2007 Aug 15;74(4):623-38. Epub 2007 May 25. PMID:17610847 doi:http://dx.doi.org/10.1016/j.bcp.2007.05.017
- ↑ Fletcher JI, Smith R, O'Donoghue SI, Nilges M, Connor M, Howden ME, Christie MJ, King GF. The structure of a novel insecticidal neurotoxin, omega-atracotoxin-HV1, from the venom of an Australian funnel web spider. Nat Struct Biol. 1997 Jul;4(7):559-66. PMID:9228949
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