Journal
BIOCHIMIE
Volume 92, Issue 12, Pages 1847-1853Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2010.08.003
Keywords
Natural toxins; alpha-KTx3; Kv1.3; Mesobuthus martensii
Categories
Funding
- National Natural Science Foundation of China [30730015, 30621003]
- Ministry of Science and Technology of China [2010CB945304]
- Bilateral Cooperation for the 16th Session of the Sino-Belgian S&T Mixed Commission
- F.W.O.-Vlaanderen [G.0330.06, G.0257.08]
- K.U.Leuven [OT-05-64]
- Interuniversity attraction Poles Program-Belgian State-Belgian Science Policy [P6/31]
- [BIL 07/10]
Ask authors/readers for more resources
Scorpion venom-derived peptidyl toxins are valuable pharmacological tools for investigating the structure function relationship of ion channels. Here, we report the purification, sequencing and functional characterization of a new K+ channel blocker (MeuKTX) from the venom of the scorpion Mesobuthus eupeus. Effects of MeuKTX on ten cloned potassium channels in Xenopus oocytes were evaluated using two-electrode voltage-clamp recordings. MeuKTX is the orthologue of BmKTX (alpha-KTx3.6), a known Kv1.3 blocker from the scorpion Mesobuthus martensii, and classified as alpha-KTx3.13. MeuKTX potently blocks rKv1.1, rKv1.2 and hKv1.3 channels with 50% inhibitory concentration (IC50) of 203.15 +/- 4.06 pM, 8.92 +/- 2.3 nM and 171 +/- 8.56 pM, respectively, but does not affect rKv1.4, rKv1.5, hKv3.1, rKv4.3, and hERG channels even at 2 mu M concentration. At this high concentration, MeuKTX is also active on rKv1.6 and Shaker IR. Our results also demonstrate that MeuKTX and BmKTX have the same channel spectrum and similar pharmacological potency. Analysis of the structure function relationships of alpha-KTx3 subfamily toxins allows us to recognize several key sites which may be useful for designing toxins with improved activity on hKv1.3, an attractive target for T-cell mediated autoimmune diseases. (C) 2010 Elsevier Masson SAS. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available