2me7: Difference between revisions
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==NMR solution structure of the GS-TAMAPIN MUTATION R6A== | ==NMR solution structure of the GS-TAMAPIN MUTATION R6A== | ||
<StructureSection load='2me7' size='340' side='right' caption='[[2me7]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | <StructureSection load='2me7' size='340' side='right'caption='[[2me7]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2me7]] 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=2ME7 OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[2me7]] 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=2ME7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2ME7 FirstGlance]. <br> | ||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ky3|2ky3]], [[2lu9|2lu9]], [[2mel|2mel]], [[2men|2men]], [[2meo|2meo]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ky3|2ky3]], [[2lu9|2lu9]], [[2mel|2mel]], [[2men|2men]], [[2meo|2meo]]</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2me7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2me7 OCA], [http://pdbe.org/2me7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2me7 RCSB], [http://www.ebi.ac.uk/pdbsum/2me7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2me7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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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/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Buthus tamalus]] | [[Category: Buthus tamalus]] | ||
[[Category: Large Structures]] | |||
[[Category: Ramirez-Cordero, B]] | [[Category: Ramirez-Cordero, B]] | ||
[[Category: Rio-Portilla, F del]] | [[Category: Rio-Portilla, F del]] | ||
Revision as of 09:22, 13 May 2020
NMR solution structure of the GS-TAMAPIN MUTATION R6ANMR solution structure of the GS-TAMAPIN MUTATION R6A
Structural highlights
Function[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.[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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