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| | ==SOLUTION STRUCTURE OF ROBUSTOXIN, THE LETHAL NEUROTOXIN FROM THE FUNNEL WEB SPIDER ATRAX ROBUSTUS, NMR, 20 STRUCTURES== | | ==SOLUTION STRUCTURE OF ROBUSTOXIN, THE LETHAL NEUROTOXIN FROM THE FUNNEL WEB SPIDER ATRAX ROBUSTUS, NMR, 20 STRUCTURES== |
| - | <StructureSection load='1qdp' size='340' side='right' caption='[[1qdp]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1qdp' size='340' side='right'caption='[[1qdp]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1qdp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atrax_robustus Atrax robustus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QDP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QDP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1qdp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Atrax_robustus Atrax robustus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QDP 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=1qdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qdp OCA], [http://pdbe.org/1qdp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1qdp RCSB], [http://www.ebi.ac.uk/pdbsum/1qdp 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=1qdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qdp OCA], [https://pdbe.org/1qdp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qdp RCSB], [https://www.ebi.ac.uk/pdbsum/1qdp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qdp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TXDT1_ATRRO TXDT1_ATRRO]] Inhibits tetrodotoxin-sensitive voltage-gated sodium channels (Nav) by binding to site 3. It slows the inactivation, causes a prolongation of action potential duration resulting in repetitive firing in autonomic and motor nerve fibers. Does not depolarize the resting potential. Does not affect tetrodotoxin-resistant sodium channels. This lethal neurotoxin is active on both insect and mammalian voltage-gated sodium channels.<ref>PMID:2728033</ref> <ref>PMID:14596608</ref> <ref>PMID:9845331</ref> <ref>PMID:9560455</ref> | + | [https://www.uniprot.org/uniprot/TXDT1_ATRRO TXDT1_ATRRO] Inhibits tetrodotoxin-sensitive voltage-gated sodium channels (Nav) by binding to site 3. It slows the inactivation, causes a prolongation of action potential duration resulting in repetitive firing in autonomic and motor nerve fibers. Does not depolarize the resting potential. Does not affect tetrodotoxin-resistant sodium channels. This lethal neurotoxin is active on both insect and mammalian voltage-gated sodium channels.<ref>PMID:2728033</ref> <ref>PMID:14596608</ref> <ref>PMID:9845331</ref> <ref>PMID:9560455</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qd/1qdp_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qd/1qdp_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </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/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </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=1qdp ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Atrax robustus]] | | [[Category: Atrax robustus]] |
| - | [[Category: Alewood, D]] | + | [[Category: Large Structures]] |
| - | [[Category: Alewood, P F]] | + | [[Category: Alewood D]] |
| - | [[Category: Norton, R S]] | + | [[Category: Alewood PF]] |
| - | [[Category: Pallaghy, P K]] | + | [[Category: Norton RS]] |
| - | [[Category: Cystine knot]] | + | [[Category: Pallaghy PK]] |
| - | [[Category: Funnel web spider]]
| + | |
| - | [[Category: Inhibitor cystine knot motif]]
| + | |
| - | [[Category: Neurotoxin]]
| + | |
| - | [[Category: Robustoxin]]
| + | |
| - | [[Category: Sodium channel modulator]]
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| - | [[Category: Venom]]
| + | |
| Structural highlights
Function
TXDT1_ATRRO Inhibits tetrodotoxin-sensitive voltage-gated sodium channels (Nav) by binding to site 3. It slows the inactivation, causes a prolongation of action potential duration resulting in repetitive firing in autonomic and motor nerve fibers. Does not depolarize the resting potential. Does not affect tetrodotoxin-resistant sodium channels. This lethal neurotoxin is active on both insect and mammalian voltage-gated sodium channels.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The solution structure of robustoxin, the lethal neurotoxin from the Sydney funnel-web spider Atrax robustus, has been determined from 2D 1H NMR data. Robustoxin is a polypeptide of 42 residues cross-linked by four disulphide bonds, the connectivities of which were determined from NMR data and trial structure calculations to be 1-15, 8-20, 14-31 and 16-42 (a 1-4/2-6/3-7/5-8 pattern). The structure consists of a small three-stranded, anti-parallel beta-sheet and a series of interlocking gamma-turns at the C-terminus. It also contains a cystine knot, thus placing it in the inhibitor cystine knot motif family of structures, which includes the omega-conotoxins and a number of plant and animal toxins and protease inhibitors. Robustoxin contains three distinct charged patches on its surface, and an extended loop that includes several aromatic and non-polar residues. Both of these structural features may play a role in its binding to the voltage-gated sodium channel.
Solution structure of robustoxin, the lethal neurotoxin from the funnel-web spider Atrax robustus.,Pallaghy PK, Alewood D, Alewood PF, Norton RS FEBS Lett. 1997 Dec 15;419(2-3):191-6. PMID:9428632[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mylecharane EJ, Spence I, Sheumack DD, Claassens R, Howden ME. Actions of robustoxin, a neurotoxic polypeptide from the venom of the male funnel-web spider (Atrax robustus), in anaesthetized monkeys. Toxicon. 1989;27(4):481-92. PMID:2728033
- ↑ Alewood D, Birinyi-Strachan LC, Pallaghy PK, Norton RS, Nicholson GM, Alewood PF. Synthesis and characterization of delta-atracotoxin-Ar1a, the lethal neurotoxin from venom of the Sydney funnel-web spider (Atrax robustus). Biochemistry. 2003 Nov 11;42(44):12933-40. PMID:14596608 doi:http://dx.doi.org/10.1021/bi030091n
- ↑ Little MJ, Wilson H, Zappia C, Cestele S, Tyler MI, Martin-Eauclaire MF, Gordon D, Nicholson GM. Delta-atracotoxins from Australian funnel-web spiders compete with scorpion alpha-toxin binding on both rat brain and insect sodium channels. FEBS Lett. 1998 Nov 20;439(3):246-52. PMID:9845331
- ↑ Nicholson GM, Walsh R, Little MJ, Tyler MI. Characterisation of the effects of robustoxin, the lethal neurotoxin from the Sydney funnel-web spider Atrax robustus, on sodium channel activation and inactivation. Pflugers Arch. 1998 Jun;436(1):117-26. PMID:9560455
- ↑ Pallaghy PK, Alewood D, Alewood PF, Norton RS. Solution structure of robustoxin, the lethal neurotoxin from the funnel-web spider Atrax robustus. FEBS Lett. 1997 Dec 15;419(2-3):191-6. PMID:9428632
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