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| | ==NMR solution structure of the GS-TAMAPIN MUTATION R13A== | | ==NMR solution structure of the GS-TAMAPIN MUTATION R13A== |
| - | <StructureSection load='2men' size='340' side='right' caption='[[2men]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2men' size='340' side='right'caption='[[2men]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2men]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buthus_tamalus Buthus tamalus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MEN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MEN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2men]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mesobuthus_tamulus Mesobuthus tamulus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MEN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MEN FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2me7|2me7]], [[2mel|2mel]], [[2meo|2meo]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2men FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2men OCA], [http://pdbe.org/2men PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2men RCSB], [http://www.ebi.ac.uk/pdbsum/2men PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2men ProSAT]</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=2men FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2men OCA], [https://pdbe.org/2men PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2men RCSB], [https://www.ebi.ac.uk/pdbsum/2men PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2men ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KAX54_MESTA KAX54_MESTA]] Blocks small conductance calcium-activated potassium channels in pyramidal neurons of the hippocampus. Displays a unique, remarkable selectivity for SK2/KCNN2 versus SK1/KCNN1 and SK3/KCNN3 channels.<ref>PMID:12239213</ref> | + | [https://www.uniprot.org/uniprot/KAX54_HOTTA KAX54_HOTTA] Blocks small conductance calcium-activated potassium channels (PubMed:12239213). Shows activity on KCa2.2/KCNN2 (IC(50)=0.0243 nM), KCa2.3/KCNN3 (IC(50)=1.7 nM), and KCa2.1/KCNN1 (IC(50)=42 nM) (PubMed:12239213). Induces cell death when tested on Jurkat E6-1 and human mammary breast cancer MDA-MB-231 which constituvely express KCa2.2/KCNN2, but not on human peripheral blood lymphocytes (which do not express KCa2.2/KCNN2) (PubMed:24821061).<ref>PMID:12239213</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==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: Buthus tamalus]] | + | [[Category: Large Structures]] |
| - | [[Category: Ramirez-Cordero, B]] | + | [[Category: Mesobuthus tamulus]] |
| - | [[Category: Rio-Portilla, F del]] | + | [[Category: Ramirez-Cordero B]] |
| - | [[Category: Alpha ktx5 4 mutant r13a]]
| + | [[Category: Del Rio-Portilla F]] |
| - | [[Category: Scorpion toxin]]
| + | |
| - | [[Category: Tamapin]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
KAX54_HOTTA Blocks small conductance calcium-activated potassium channels (PubMed:12239213). Shows activity on KCa2.2/KCNN2 (IC(50)=0.0243 nM), KCa2.3/KCNN3 (IC(50)=1.7 nM), and KCa2.1/KCNN1 (IC(50)=42 nM) (PubMed:12239213). Induces cell death when tested on Jurkat E6-1 and human mammary breast cancer MDA-MB-231 which constituvely express KCa2.2/KCNN2, but not on human peripheral blood lymphocytes (which do not express KCa2.2/KCNN2) (PubMed:24821061).[1]
Publication Abstract from PubMed
The scorpion toxin tamapin displays the most potent and selective blockage against KCa2.2 channels known to date. In this work, we report the biosynthesis, three-dimensional structure, and cytotoxicity on cancer cell lines (Jurkat E6-1 and human mammary breast cancer MDA-MB-231) of recombinant tamapin and five related peptides bearing mutations on residues (R6A,R7A, R13A, R6A-R7A, and GS-tamapin) that were previously suggested to be important for tamapin's activity. The indicated cell lines were used as they constitutively express KCa2.2 channels. The studied toxin-like peptides displayed lethal responses on Jurkat T cells and breast cancer cells; their effect is dose- and time-dependent with IC50 values in the nanomolar range. The order of potency is r-tamapin > GS-tamapin > R6A > R13A > R6A-R7A > R7A for Jurkat T cells and r-tamapin > R7A for MDA-MB-231 breast cancer cells. Our structural determination by NMR demonstrated that r-tamapin preserves the folding of the alphaKTx5 subfamily and that neither single nor double alanine mutations affect the three-dimensional structure of the wild-type peptide. In contrast, our activity assays show that changes in cytotoxicity are related to the chemical nature of certain residues. Our results suggest that the toxic activity of r-tamapin on Jurkat and breast cancer cells could be mediated by the interaction of charged residues in tamapin with KCa2.2 channels via the apoptotic cell death pathway.
Cytotoxicity of Recombinant Tamapin and Related Toxin-Like Peptides on Model Cell Lines.,Ramirez-Cordero B, Toledano Y, Cano-Sanchez P, Hernandez-Lopez R, Flores-Solis D, Saucedo-Yanez AL, Chavez-Uribe I, Brieba LG, Del Rio-Portilla F Chem Res Toxicol. 2014 May 12. PMID:24821061[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pedarzani P, D'hoedt D, Doorty KB, Wadsworth JD, Joseph JS, Jeyaseelan K, Kini RM, Gadre SV, Sapatnekar SM, Stocker M, Strong PN. Tamapin, a venom peptide from the Indian red scorpion (Mesobuthus tamulus) that targets small conductance Ca2+-activated K+ channels and afterhyperpolarization currents in central neurons. J Biol Chem. 2002 Nov 29;277(48):46101-9. Epub 2002 Sep 17. PMID:12239213 doi:http://dx.doi.org/10.1074/jbc.M206465200
- ↑ Ramirez-Cordero B, Toledano Y, Cano-Sanchez P, Hernandez-Lopez R, Flores-Solis D, Saucedo-Yanez AL, Chavez-Uribe I, Brieba LG, Del Rio-Portilla F. Cytotoxicity of Recombinant Tamapin and Related Toxin-Like Peptides on Model Cell Lines. Chem Res Toxicol. 2014 May 12. PMID:24821061 doi:http://dx.doi.org/10.1021/tx4004193
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