Referenced in: none

Automatically associated channels: Kv11.1

Title: A common "hot spot" confers hERG blockade activity to alpha-scorpion toxins affecting K+ channels.

Authors: Yousra Abdel-Mottaleb, Gerardo Corzo, Marie-France Martin-Eauclaire, Honoo Satake, Brigitte Céard, Steve Peigneur, Praveen Nambaru, Pierre-Edouard Bougis, Lourival D Possani, Jan Tytgat

Journal, date & volume: Biochem. Pharmacol., 2008 Sep 15 , 76, 805-15

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18687312

Abstract
While alpha-KTx peptides are generally known for their modulation of the Shaker-type and the Ca(2+)-activated potassium channels, gamma-KTxs are associated with hERG channels modulation. An exception to the rule is BmTx3 which belongs to subfamily alpha-KTx15 and can block hERG channels. To explain the peculiar behavior of BmTx3, a tentative "hot spot" formed of 2 basic residues (R18 and K19) was suggested but never further studied [Huys I, et al. BmTx3, a scorpion toxin with two putative functional faces separately active on A-type K(+) and HERG currents. Biochem J 2004;378:745-52]. In this work, we investigated if the "hot spot" is a commonality in subfamily alpha-KTx15 by testing the effect of (AmmTx3, Aa1, discrepin). Furthermore, single mutations altering the "hot spot" in discrepin, have introduced for the very first time a hERG blocking activity to a previously non-active alpha-KTx. Additionally, we could extend our results to other alpha-KTx subfamily members belonging to alpha-KTx1, 4 and 6, therefore, the "hot spot" represents a common pharmacophore serving as a predictive tool for yet to be discovered alpha-KTxs.