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==High resolution x-ray structure of racemic ShK toxin==
==High resolution x-ray structure of racemic ShK toxin==
<StructureSection load='4lfs' size='340' side='right' caption='[[4lfs]], [[Resolution|resolution]] 0.97&Aring;' scene=''>
<StructureSection load='4lfs' size='340' side='right'caption='[[4lfs]], [[Resolution|resolution]] 0.97&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4lfs]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LFS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LFS FirstGlance]. <br>
<table><tr><td colspan='2'>[[4lfs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Stichodactyla_helianthus Stichodactyla helianthus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LFS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LFS FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 0.97&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lfq|4lfq]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=4lfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lfs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lfs RCSB], [http://www.ebi.ac.uk/pdbsum/4lfs PDBsum]</span></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=4lfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lfs OCA], [https://pdbe.org/4lfs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lfs RCSB], [https://www.ebi.ac.uk/pdbsum/4lfs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lfs ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/K1A_STIHL K1A_STIHL] Inhibits voltage-dependent potassium channels. Inhibits Kv1.3/KCNA3 potently and also blocks Kv1.1/KCNA1, Kv1.4/KCNA4, and Kv1.6/KCNA6 at subnanomolar concentrations.<ref>PMID:7660365</ref>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 4lfs" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Potassium channel toxin|Potassium channel toxin]]
*[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bezanilla, F]]
[[Category: Large Structures]]
[[Category: Dang, B]]
[[Category: Stichodactyla helianthus]]
[[Category: Kent, S B.H]]
[[Category: Bezanilla F]]
[[Category: Kubota, T]]
[[Category: Dang B]]
[[Category: Mandal, K]]
[[Category: Kent SBH]]
[[Category: Chemical protein synthesis]]
[[Category: Kubota T]]
[[Category: Racemic protein crystallography]]
[[Category: Mandal K]]
[[Category: Shk toxin]]
[[Category: Toxin]]

Latest revision as of 03:36, 28 December 2023

High resolution x-ray structure of racemic ShK toxinHigh resolution x-ray structure of racemic ShK toxin

Structural highlights

4lfs is a 1 chain structure with sequence from Stichodactyla helianthus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 0.97Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

K1A_STIHL Inhibits voltage-dependent potassium channels. Inhibits Kv1.3/KCNA3 potently and also blocks Kv1.1/KCNA1, Kv1.4/KCNA4, and Kv1.6/KCNA6 at subnanomolar concentrations.[1]

Publication Abstract from PubMed

We have re-examined the utility of native chemical ligation at -Gln/Glu-Cys- [Glx-Cys] and -Asn/Asp-Cys- [Asx-Cys] sites. Using the improved thioaryl catalyst 4-mercaptophenylacetic acid (MPAA), native chemical ligation could be performed at -Gln-Cys- and Asn-Cys- sites without side reactions. After optimization, ligation at a -Glu-Cys- site could also be used as a ligation site, with minimal levels of byproduct formation. However, -Asp-Cys- is not appropriate for use as a site for native chemical ligation because of formation of significant amounts of beta-linked byproduct. The feasibility of native chemical ligation at -Gln-Cys- enabled a convergent total chemical synthesis of the enantiomeric forms of the ShK toxin protein molecule. The d-ShK protein molecule was approximately 50,000-fold less active in blocking the Kv1.3 channel than the l-ShK protein molecule. Racemic protein crystallography was used to obtain high-resolution X-ray diffraction data for ShK toxin. The structure was solved by direct methods and showed significant differences from the previously reported NMR structures in some regions of the ShK protein molecule.

Native Chemical Ligation at Asx-Cys, Glx-Cys: Chemical Synthesis and High-Resolution X-ray Structure of ShK Toxin by Racemic Protein Crystallography.,Dang B, Kubota T, Mandal K, Bezanilla F, Kent SB J Am Chem Soc. 2013 Aug 6. PMID:23919482[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Castaneda O, Sotolongo V, Amor AM, Stocklin R, Anderson AJ, Harvey AL, Engstrom A, Wernstedt C, Karlsson E. Characterization of a potassium channel toxin from the Caribbean Sea anemone Stichodactyla helianthus. Toxicon. 1995 May;33(5):603-13. PMID:7660365
  2. Dang B, Kubota T, Mandal K, Bezanilla F, Kent SB. Native Chemical Ligation at Asx-Cys, Glx-Cys: Chemical Synthesis and High-Resolution X-ray Structure of ShK Toxin by Racemic Protein Crystallography. J Am Chem Soc. 2013 Aug 6. PMID:23919482 doi:10.1021/ja4046795

4lfs, resolution 0.97Å

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