2meo: Difference between revisions
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''' | ==NMR solution structure of the double GS-Tamapin mutation R6A/R7A== | ||
<StructureSection load='2meo' size='340' side='right' caption='[[2meo]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2meo]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MEO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MEO FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2me7|2me7]], [[2mel|2mel]], [[2men|2men]]</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2meo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2meo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2meo RCSB], [http://www.ebi.ac.uk/pdbsum/2meo PDBsum]</span></td></tr> | |||
<table> | |||
<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> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Ramirez-Cordero, B.]] | |||
[[Category: Rio-Portilla, F del.]] | |||
[[Category: Alpha ktx5 4 double mutant r6a r7a]] | |||
[[Category: Scorpion toxin]] | |||
[[Category: Tamapin]] | |||
[[Category: Toxin]] | |||