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| | ==SOLUTION STRUCTURE OF HANATOXIN 1== | | ==SOLUTION STRUCTURE OF HANATOXIN 1== |
| - | <StructureSection load='1d1h' size='340' side='right'caption='[[1d1h]], [[NMR_Ensembles_of_Models | 21 NMR models]]' scene=''> | + | <StructureSection load='1d1h' size='340' side='right'caption='[[1d1h]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[1d1h]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Grammostola_rosea Grammostola rosea]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D1H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D1H FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1d1h]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Grammostola_rosea Grammostola rosea]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D1H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D1H 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=1d1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d1h OCA], [https://pdbe.org/1d1h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1d1h RCSB], [https://www.ebi.ac.uk/pdbsum/1d1h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1d1h 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=1d1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d1h OCA], [https://pdbe.org/1d1h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1d1h RCSB], [https://www.ebi.ac.uk/pdbsum/1d1h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1d1h ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TXHN1_GRARO TXHN1_GRARO]] Inhibits Kv2.1/KCNB1 and Kv4.2/KCND2 voltage-gated potassium channels. Acts as a gating modifier by shifting channel openings to more depolarized voltages and acts via the occupancy of multiple binding sites on the channel. The toxin binding sites are situated on the S3-S4 extracellular linker of the channel. At least two hanatoxin molecules can occupy the Kv2.1/KCNB1 channel, and maybe more (three or four). Can also inhibit calcium channels (Cav2.1/CACNA1A). Needs to partition into the membrane in order to bind to the channel.<ref>PMID:17101164</ref> <ref>PMID:9136774</ref> <ref>PMID:9136775</ref> <ref>PMID:9671721</ref>
| + | [https://www.uniprot.org/uniprot/TXHN1_GRARO TXHN1_GRARO] Inhibits Kv2.1/KCNB1 and Kv4.2/KCND2 voltage-gated potassium channels. Acts as a gating modifier by shifting channel openings to more depolarized voltages and acts via the occupancy of multiple binding sites on the channel. The toxin binding sites are situated on the S3-S4 extracellular linker of the channel. At least two hanatoxin molecules can occupy the Kv2.1/KCNB1 channel, and maybe more (three or four). Can also inhibit calcium channels (Cav2.1/CACNA1A). Needs to partition into the membrane in order to bind to the channel.<ref>PMID:17101164</ref> <ref>PMID:9136774</ref> <ref>PMID:9136775</ref> <ref>PMID:9671721</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | [[Category: Grammostola rosea]] | | [[Category: Grammostola rosea]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kim, J I]] | + | [[Category: Kim JI]] |
| - | [[Category: Sato, K]] | + | [[Category: Sato K]] |
| - | [[Category: Shimada, I]] | + | [[Category: Shimada I]] |
| - | [[Category: Swartz, K J]] | + | [[Category: Swartz KJ]] |
| - | [[Category: Takahashi, H]] | + | [[Category: Takahashi H]] |
| - | [[Category: Cystine knot]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
TXHN1_GRARO Inhibits Kv2.1/KCNB1 and Kv4.2/KCND2 voltage-gated potassium channels. Acts as a gating modifier by shifting channel openings to more depolarized voltages and acts via the occupancy of multiple binding sites on the channel. The toxin binding sites are situated on the S3-S4 extracellular linker of the channel. At least two hanatoxin molecules can occupy the Kv2.1/KCNB1 channel, and maybe more (three or four). Can also inhibit calcium channels (Cav2.1/CACNA1A). Needs to partition into the membrane in order to bind to the channel.[1] [2] [3] [4]
Publication Abstract from PubMed
The three-dimensional structure of hanatoxin1 (HaTx1) was determined by using NMR spectroscopy. HaTx1 is a 35 amino acid residue peptide toxin that inhibits the drk1 voltage-gated K(+) channel not by blocking the pore, but by altering the energetics of gating. Both the amino acid sequence of HaTx1 and its unique mechanism of action distinguish this toxin from the previously described K(+) channel inhibitors. Unlike most other K(+) channel-blocking toxins, HaTx1 adopts an "inhibitor cystine knot" motif and is composed of two beta-strands, strand I for residues 19-21 and strand II for residues 28-30, connected by four chain reversals. A comparison of the surface features of HaTx1 with those of other gating modifier toxins of voltage-gated Ca(2+) and Na(+) channels suggests that the combination of a hydrophobic patch and surrounding charged residues is principally responsible for the binding of gating modifier toxins to voltage-gated ion channels.
Solution structure of hanatoxin1, a gating modifier of voltage-dependent K(+) channels: common surface features of gating modifier toxins.,Takahashi H, Kim JI, Min HJ, Sato K, Swartz KJ, Shimada I J Mol Biol. 2000 Mar 31;297(3):771-80. PMID:10731427[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Herrington J. Gating modifier peptides as probes of pancreatic beta-cell physiology. Toxicon. 2007 Feb;49(2):231-8. Epub 2006 Sep 23. PMID:17101164 doi:http://dx.doi.org/S0041-0101(06)00354-0
- ↑ Swartz KJ, MacKinnon R. Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites. Neuron. 1997 Apr;18(4):665-73. PMID:9136774
- ↑ Swartz KJ, MacKinnon R. Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels. Neuron. 1997 Apr;18(4):675-82. PMID:9136775
- ↑ Li-Smerin Y, Swartz KJ. Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8585-9. PMID:9671721
- ↑ Takahashi H, Kim JI, Min HJ, Sato K, Swartz KJ, Shimada I. Solution structure of hanatoxin1, a gating modifier of voltage-dependent K(+) channels: common surface features of gating modifier toxins. J Mol Biol. 2000 Mar 31;297(3):771-80. PMID:10731427 doi:http://dx.doi.org/10.1006/jmbi.2000.3609
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