2ca7: Difference between revisions

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New page: left|200px<br /><applet load="2ca7" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ca7" /> '''CONKUNITZIN-S1 IS THE FIRST MEMBER OF A NEW ...
 
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[[Image:2ca7.gif|left|200px]]<br /><applet load="2ca7" size="450" color="white" frame="true" align="right" spinBox="true"
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'''CONKUNITZIN-S1 IS THE FIRST MEMBER OF A NEW KUNITZ-TYPE NEUROTOXIN FAMILY- STRUCTURAL AND FUNCTIONAL CHARACTERIZATION'''<br />


==Overview==
==Conkunitzin-S1 Is The First Member Of A New Kunitz-Type Neurotoxin Family- Structural and Functional Characterization==
Conkunitzin-S1 (Conk-S1) is a 60-residue neurotoxin from the venom of the, cone snail Conus striatus that interacts with voltage-gated potassium, channels. Conk-S1 shares sequence homology with Kunitz-type proteins but, contains only two out of the three highly conserved cysteine bridges, which are typically found in these small, basic protein modules. In this, study the three-dimensional structure of Conk-S1 has been solved by, multidimensional NMR spectroscopy. The solution structure of recombinant, Conk-S1 shows that a Kunitz fold is present, even though one of the highly, conserved disulfide cross-links is missing. Introduction of a third, homologous disulfide bond into Conk-S1 results in a functional toxin with, similar affinity for Shaker potassium channels. The affinity of Conk-S1, can be enhanced by a pore mutation within the Shaker channel pore, indicating an interaction of Conk-S1 with the vestibule of potassium, channels.
<StructureSection load='2ca7' size='340' side='right'caption='[[2ca7]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ca7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_striatus Conus striatus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1yl2 1yl2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CA7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CA7 FirstGlance]. <br>
</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=2ca7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ca7 OCA], [https://pdbe.org/2ca7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ca7 RCSB], [https://www.ebi.ac.uk/pdbsum/2ca7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ca7 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/VKTS1_CONST VKTS1_CONST] Blocks specifically voltage-activated potassium channels (Kv) of the Shaker family (IC(50)=1.33 nM).<ref>PMID:15833744</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ca/2ca7_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </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/main_output.php?pdb_ID=2ca7 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Conkunitzin-S1 (Conk-S1) is a 60-residue neurotoxin from the venom of the cone snail Conus striatus that interacts with voltage-gated potassium channels. Conk-S1 shares sequence homology with Kunitz-type proteins but contains only two out of the three highly conserved cysteine bridges, which are typically found in these small, basic protein modules. In this study the three-dimensional structure of Conk-S1 has been solved by multidimensional NMR spectroscopy. The solution structure of recombinant Conk-S1 shows that a Kunitz fold is present, even though one of the highly conserved disulfide cross-links is missing. Introduction of a third, homologous disulfide bond into Conk-S1 results in a functional toxin with similar affinity for Shaker potassium channels. The affinity of Conk-S1 can be enhanced by a pore mutation within the Shaker channel pore indicating an interaction of Conk-S1 with the vestibule of potassium channels.


==About this Structure==
Conkunitzin-S1 is the first member of a new Kunitz-type neurotoxin family. Structural and functional characterization.,Bayrhuber M, Vijayan V, Ferber M, Graf R, Korukottu J, Imperial J, Garrett JE, Olivera BM, Terlau H, Zweckstetter M, Becker S J Biol Chem. 2005 Jun 24;280(25):23766-70. Epub 2005 Apr 15. PMID:15833744<ref>PMID:15833744</ref>
2CA7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Conus_striatus Conus striatus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CA7 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Conkunitzin-S1 is the first member of a new Kunitz-type neurotoxin family. Structural and functional characterization., Bayrhuber M, Vijayan V, Ferber M, Graf R, Korukottu J, Imperial J, Garrett JE, Olivera BM, Terlau H, Zweckstetter M, Becker S, J Biol Chem. 2005 Jun 24;280(25):23766-70. Epub 2005 Apr 15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15833744 15833744]
</div>
<div class="pdbe-citations 2ca7" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Conus striatus]]
[[Category: Conus striatus]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Bayrhuber, M.]]
[[Category: Bayrhuber M]]
[[Category: Becker, S.]]
[[Category: Becker S]]
[[Category: Ferber, M]]
[[Category: Ferber M]]
[[Category: Garrett, J.E.]]
[[Category: Garrett JE]]
[[Category: Graf, R.]]
[[Category: Graf R]]
[[Category: Imperial, J.]]
[[Category: Imperial J]]
[[Category: Korukottu, J.]]
[[Category: Korukottu J]]
[[Category: Olivera, B.M.]]
[[Category: Olivera BM]]
[[Category: Terlau, H.]]
[[Category: Terlau H]]
[[Category: Vijayan, V.]]
[[Category: Vijayan V]]
[[Category: Zweckstetter, M.]]
[[Category: Zweckstetter M]]
[[Category: conkunitzin]]
[[Category: kunitz-domain]]
[[Category: kunitz-type fold]]
[[Category: neurotoxin]]
[[Category: potassium channel inhibitor]]
[[Category: toxin]]
 
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Latest revision as of 11:25, 22 May 2024

Conkunitzin-S1 Is The First Member Of A New Kunitz-Type Neurotoxin Family- Structural and Functional Characterization

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