PDBsum entry 2lu9

Toxin

PDB id: 2lu9

Contents

Protein chain

31 a.a.

PDB id:

2lu9

Name:

Toxin

Title:

Nmr solution structure of recombinant tamapin

Structure:

Potassium channel toxin alpha-ktx 5.4. Chain: a. Synonym: tamapin. Engineered: yes

Source:

Mesobuthus tamulus. Eastern indian scorpion. Organism_taxid: 34647

NMR struc:

18 models

Authors:

F.Del Rio-Portilla,B.Ramirez-Cordero

Key ref:

B.Ramírez-Cordero et al. (2014). Cytotoxicity of recombinant tamapin and related toxin-like peptides on model cell lines. Chem Res Toxicol, 27, 960-967. PubMed id: 24821061 DOI: 10.1021/tx4004193

Date:

08-Jun-12 Release date: 11-Dec-13

Protein chain

P59869  (KAX54_HOTTA) -  Potassium channel toxin alpha-KTx 5.4 from Hottentotta tamulus

Seq: 31 a.a.

Struc: 31 a.a.

DOI no: 10.1021/tx4004193

Chem Res Toxicol 27:960-967 (2014)

PubMed id: 24821061

Cytotoxicity of recombinant tamapin and related toxin-like peptides on model cell lines.

B.Ramírez-Cordero, Y.Toledano, P.Cano-Sánchez, R.Hernández-López, D.Flores-Solis, A.L.Saucedo-Yáñez, I.Chávez-Uribe, L.G.Brieba, F.del Río-Portilla.

ABSTRACT

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 αKTx5 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.