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| | ==THREE-DIMENSIONAL STRUCTURE IN SOLUTION OF THE SODIUM CHANNEL AGONIST/ANTAGONIST DELTA-CONOTOXIN TXVIA== | | ==THREE-DIMENSIONAL STRUCTURE IN SOLUTION OF THE SODIUM CHANNEL AGONIST/ANTAGONIST DELTA-CONOTOXIN TXVIA== |
| - | <StructureSection load='1fu3' size='340' side='right'caption='[[1fu3]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1fu3' size='340' side='right'caption='[[1fu3]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1fu3]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FU3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FU3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1fu3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_textile Conus textile]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FU3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FU3 FirstGlance]. <br> |
| - | </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=1fu3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fu3 OCA], [https://pdbe.org/1fu3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fu3 RCSB], [https://www.ebi.ac.uk/pdbsum/1fu3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fu3 ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1fu3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fu3 OCA], [https://pdbe.org/1fu3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fu3 RCSB], [https://www.ebi.ac.uk/pdbsum/1fu3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fu3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CO16A_CONTE CO16A_CONTE]] Delta-conotoxins bind to site 6 of voltage-gated sodium channels (Nav) and inhibit the inactivation process. Binding of this toxin is strongly calcium-dependent but not voltage-dependent. The binding site is most likely on the extracellular side of the sodium channel. Binds receptor sites on both mollusk and rat central nervous system, but despite its high affinity binding to rat sodium channel, it has no functional effect in vivo and in vitro on it. Has also no effect on Gambusia fish. Is important in mollusk for the paralysis of the prey. Upon injection of the peptide, a subordinate lobster assumes an exaggerated dominant posture (of a 'King-Kong' lobster!).
| + | [https://www.uniprot.org/uniprot/O16A_CONTE O16A_CONTE] Delta-conotoxins bind to site 6 of voltage-gated sodium channels (Nav) and inhibit the inactivation process. Binding of this toxin is strongly calcium-dependent but not voltage-dependent. The binding site is most likely on the extracellular side of the sodium channel. Binds receptor sites on both mollusk and rat central nervous system, but despite its high affinity binding to rat sodium channel, it has no functional effect in vivo and in vitro on it. Has also no effect on Gambusia fish. Is important in mollusk for the paralysis of the prey. Upon injection of the peptide, a subordinate lobster assumes an exaggerated dominant posture (of a 'King-Kong' lobster!).<ref>PMID:1761058</ref> <ref>PMID:2706261</ref> <ref>PMID:8261090</ref> <ref>PMID:8300586</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Conus textile]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fainzilber, M]] | + | [[Category: Fainzilber M]] |
| - | [[Category: Kohno, T]] | + | [[Category: Kohno T]] |
| - | [[Category: Sasaki, T]] | + | [[Category: Sasaki T]] |
| - | [[Category: Sato, K]] | + | [[Category: Sato K]] |
| - | [[Category: Cystine knot motif]]
| + | |
| - | [[Category: Delta-conotoxin]]
| + | |
| - | [[Category: Metal transport inhibitor]]
| + | |
| - | [[Category: Triple-stranded]]
| + | |
| Structural highlights
Function
O16A_CONTE Delta-conotoxins bind to site 6 of voltage-gated sodium channels (Nav) and inhibit the inactivation process. Binding of this toxin is strongly calcium-dependent but not voltage-dependent. The binding site is most likely on the extracellular side of the sodium channel. Binds receptor sites on both mollusk and rat central nervous system, but despite its high affinity binding to rat sodium channel, it has no functional effect in vivo and in vitro on it. Has also no effect on Gambusia fish. Is important in mollusk for the paralysis of the prey. Upon injection of the peptide, a subordinate lobster assumes an exaggerated dominant posture (of a 'King-Kong' lobster!).[1] [2] [3] [4]
Publication Abstract from PubMed
The three-dimensional solution structure of delta-conotoxin TxVIA, a 27-mer peptide agonist/antagonist of sodium channels, was determined by two-dimensional (1)H NMR spectroscopy with simulated annealing calculations. A total of 20 converged structures of delta-conotoxin TxVIA were obtained on the basis of 360 distance constraints obtained from nuclear Overhauser effect connectivities, 28 torsion angle constraints, and 27 constraints associated with hydrogen bonds and disulfide bonds. The atomic root mean square difference about the averaged coordinate positions is 0.35 +/- 0.07 A for the backbone atoms (N, C(alpha), C) and 0.98 +/- 0.14 A for all heavy atoms of the entire peptide. The molecular structure of delta-conotoxin TxVIA is composed of a short triple-stranded antiparallel beta-sheet. The overall beta-sheet topology is +2x, -1, which is the same as those for other conotoxins. However, the three-dimensional structure of delta-conotoxin TxVIA has an unusual hydrophobic patch on one side of the molecule, which may play an important role in the sodium channel binding. These results provide a molecular basis for understanding the mechanism of sodium channel modulation through the toxin-channel interaction and insight into the discrimination of different ion channels.
Three-dimensional solution structure of the sodium channel agonist/antagonist delta-conotoxin TxVIA.,Kohno T, Sasaki T, Kobayashi K, Fainzilber M, Sato K J Biol Chem. 2002 Sep 27;277(39):36387-91. Epub 2002 Jul 26. PMID:12145313[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fainzilber M, Gordon D, Hasson A, Spira ME, Zlotkin E. Mollusc-specific toxins from the venom of Conus textile neovicarius. Eur J Biochem. 1991 Dec 5;202(2):589-95. PMID:1761058 doi:10.1111/j.1432-1033.1991.tb16412.x
- ↑ Hillyard DR, Olivera BM, Woodward S, Corpuz GP, Gray WR, Ramilo CA, Cruz LJ. A molluscivorous Conus toxin: conserved frameworks in conotoxins. Biochemistry. 1989 Jan 10;28(1):358-61. PMID:2706261 doi:10.1021/bi00427a049
- ↑ Hasson A, Fainzilber M, Gordon D, Zlotkin E, Spira ME. Alteration of sodium currents by new peptide toxins from the venom of a molluscivorous Conus snail. Eur J Neurosci. 1993 Jan 1;5(1):56-64. PMID:8261090 doi:10.1111/j.1460-9568.1993.tb00205.x
- ↑ Fainzilber M, Kofman O, Zlotkin E, Gordon D. A new neurotoxin receptor site on sodium channels is identified by a conotoxin that affects sodium channel inactivation in molluscs and acts as an antagonist in rat brain. J Biol Chem. 1994 Jan 28;269(4):2574-80 PMID:8300586
- ↑ Kohno T, Sasaki T, Kobayashi K, Fainzilber M, Sato K. Three-dimensional solution structure of the sodium channel agonist/antagonist delta-conotoxin TxVIA. J Biol Chem. 2002 Sep 27;277(39):36387-91. Epub 2002 Jul 26. PMID:12145313 doi:10.1074/jbc.M206833200
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