2ky3: Difference between revisions
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< | ==Solution structure of GS-alfa-Ktx5.4 synthetic scorpion like== | ||
<StructureSection load='2ky3' size='340' side='right'caption='[[2ky3]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2ky3]] 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=2KY3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KY3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 17 models</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=2ky3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ky3 OCA], [https://pdbe.org/2ky3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ky3 RCSB], [https://www.ebi.ac.uk/pdbsum/2ky3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ky3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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;"> | |||
== 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<ref>PMID:24821061</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2ky3" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
[[ | *[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mesobuthus tamulus]] | [[Category: Mesobuthus tamulus]] | ||
[[Category: | [[Category: Brieba-De Castro L]] | ||
[[Category: | [[Category: Del Rio-Portilla F]] | ||
[[Category: | [[Category: Ramirez-Cordero BE]] | ||
Latest revision as of 04:08, 21 November 2024
Solution structure of GS-alfa-Ktx5.4 synthetic scorpion likeSolution structure of GS-alfa-Ktx5.4 synthetic scorpion like
Structural highlights
FunctionKAX54_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 PubMedThe 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 AlsoReferences
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