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==SOLUTION STRUCTURE OF HONGOTOXIN 1==
==SOLUTION STRUCTURE OF HONGOTOXIN 1==
<StructureSection load='1hly' size='340' side='right'caption='[[1hly]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''>
<StructureSection load='1hly' size='340' side='right'caption='[[1hly]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1hly]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bark_scorpion Bark scorpion]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HLY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HLY FirstGlance]. <br>
<table><tr><td colspan='2'>[[1hly]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Centruroides_limbatus Centruroides limbatus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HLY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HLY 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=1hly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hly OCA], [https://pdbe.org/1hly PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hly RCSB], [https://www.ebi.ac.uk/pdbsum/1hly PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hly 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=1hly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hly OCA], [https://pdbe.org/1hly PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hly RCSB], [https://www.ebi.ac.uk/pdbsum/1hly PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hly ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/KAX25_CENLM KAX25_CENLM]] Potent selective inhibitor of Kv1.1/KCNA1, Kv1.2/KCNA2, Kv1.3/KCNA3 voltage-gated potassium channels. Weak inhibitor of Kv1.6/KCNA6 potassium channel.<ref>PMID:9446567</ref>
[https://www.uniprot.org/uniprot/KAX25_CENLM KAX25_CENLM] Potent selective inhibitor of Kv1.1/KCNA1, Kv1.2/KCNA2, Kv1.3/KCNA3 voltage-gated potassium channels. Weak inhibitor of Kv1.6/KCNA6 potassium channel.<ref>PMID:9446567</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=1hly 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=1hly ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Hongotoxin(1) (HgTX(1)), a 39-residue peptide recently isolated from the venom of Centruroides limbatus, blocks the voltage-gated K+ channels K(v)1.1, K(v)1.2, and K(v)1.3 at picomolar toxin concentrations (Koschak, A., Bugianesi, R. M., Mitterdorfer, J., Kaczorowski, G. J., Garcia, M. L., and Knaus, H. G. (1998) J. Biol. Chem. 273, 2639-2644). In this report, we determine the three-dimensional structure of HgTX(1) using NMR spectroscopy (PDB-code: 1HLY). HgTX(1) was found to possess a structure similar to previously characterized K+ channel toxins (e.g. margatoxin) consisting of a three-stranded antiparallel beta-sheet (residues 2-4, 26-30, and 33-37) and a helical conformation (part 3(10) helix and part alpha helix; residues 10-20). Due to the importance of residue Lys-28 for high-affinity interaction with the respective channels, lysine-reactive fluorescence dyes cannot be used to label wild-type HgTX(1). On the basis of previous studies (see above) and our NMR data, a HgTX(1) mutant (HgTX(1)-A19C) was engineered, expressed, and purified. HgTX(1)-A19C-SH was labeled using sulfhydryl-reactive Cy3-, Cy5-, and Alexa-dyes. Pharmacological characterization of fluorescently labeled HgTX(1)-A19C in radioligand binding studies indicated that these hongotoxin(1) analogues retain high-affinity for voltage-gated K+ channels and a respective pharmacological profile. Cy3- and Alexa-dye-labeled hongotoxin(1) analogues were used to investigate the localization of K+ channels in brain sections. The distribution of toxin binding closely follows the distribution of K(v)1.2 immunoreactivity with the highest expression levels in the cerebellar Purkinje cell layer. Taken together, these results demonstrate that fluorescently labeled HgTX(1) analogues comprise novel probes to characterize a subset of voltage-gated K+ channels.
Synthesis, characterization, and application of cy-dye- and alexa-dye-labeled hongotoxin(1) analogues. The first high affinity fluorescence probes for voltage-gated K+ channels.,Pragl B, Koschak A, Trieb M, Obermair G, Kaufmann WA, Gerster U, Blanc E, Hahn C, Prinz H, Schutz G, Darbon H, Gruber HJ, Knaus HG Bioconjug Chem. 2002 May-Jun;13(3):416-25. PMID:12009929<ref>PMID:12009929</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1hly" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bark scorpion]]
[[Category: Centruroides limbatus]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Blanc, E]]
[[Category: Blanc E]]
[[Category: Darbon, H]]
[[Category: Darbon H]]
[[Category: Gerster, U]]
[[Category: Gerster U]]
[[Category: Gruber, H J]]
[[Category: Gruber HJ]]
[[Category: Hahn, C]]
[[Category: Hahn C]]
[[Category: Kaufmann, W A]]
[[Category: Kaufmann WA]]
[[Category: Knaus, H G]]
[[Category: Knaus HG]]
[[Category: Koschak, A]]
[[Category: Koschak A]]
[[Category: Obermair, G]]
[[Category: Obermair G]]
[[Category: Pragl, B]]
[[Category: Pragl B]]
[[Category: Prinz, H]]
[[Category: Prinz H]]
[[Category: Schutz, G]]
[[Category: Schutz G]]
[[Category: Trieb, M]]
[[Category: Trieb M]]
[[Category: Centruroides limbatus hgtx1]]
[[Category: Potassium channel]]
[[Category: Scorpion]]
[[Category: Toxin]]
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