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http://hdl.handle.net/1942/13605
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DC Field | Value | Language |
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dc.contributor.author | Vandendriessche, Thomas | - |
dc.contributor.author | Kopljar, Ivan | - |
dc.contributor.author | Jenkins, David Paul | - |
dc.contributor.author | Diego-Garcia, Elia | - |
dc.contributor.author | Abdel-Mottaleb, Yousra | - |
dc.contributor.author | Vermassen, Elke | - |
dc.contributor.author | CLYNEN, Elke | - |
dc.contributor.author | Schoofs, Liliane | - |
dc.contributor.author | Wulff, Heike | - |
dc.contributor.author | Snyders, Dirk | - |
dc.contributor.author | Tytgat, Jan | - |
dc.date.accessioned | 2012-04-27T13:39:54Z | - |
dc.date.available | 2012-04-27T13:39:54Z | - |
dc.date.issued | 2012 | - |
dc.identifier.citation | BIOCHEMICAL PHARMACOLOGY, 83 (9), p. 1307-1317 | - |
dc.identifier.issn | 0006-2952 | - |
dc.identifier.uri | http://hdl.handle.net/1942/13605 | - |
dc.description.abstract | Given their medical importance, most attention has been paid toward the venom composition of scorpions of the Buthidae family. Nevertheless, research has shown that the venom of scorpions of other families is also a remarkable source of unique peptidyl toxins. The kappa-KTx family of voltage-gated potassium channel (VGPC) scorpion toxins is hereof an example. From the telson of the scorpion Heterometrus laoticus (Scorpionidae), a peptide, HelaTx1, with unique primary sequence was purified through HPLC and sequenced by Edman degradation. Based on the amino acid sequence, the peptide could be cloned and the cDNA sequence revealed. HelaTx1 was chemically synthesized and functionally characterized on VGPCs of the Shaker-related, Shab-related, Shaw-related and Shal-related subfamilies. Furthermore, the toxin was also tested on small- and intermediate conductance Ca2+-activated K+ channels. From the channels studied, K(v)1.1 and K(v)1.6 were found to be the most sensitive (K(v)1.1 EC50 = 9.9 +/- 1.6 mu M). The toxin did not alter the activation of the channels. Competition experiments with TEA showed that the toxin is a pore blocker. Mutational studies showed that the residues E353 and Y379 in the pore of K(v)1.1 act as major interaction points for binding of the toxin. Given the amino acid sequence, the predicted secondary structure and the biological activity on VGPCs, HelaTx1 should be included in the kappa-KTX family. Based on a phylogenetic study, we rearranged this family of VGPC toxins into five subfamilies and suggest that HelaTx1 is the first member of the new kappa-KTx5 subfamily. (C) 2012 Elsevier Inc. All rights reserved. | - |
dc.description.sponsorship | We are thankful to Maria L. Garcia, Merck Research Laboratories, USA for sharing K<INF>v</INF>1.3. We are also grateful to L Prendini, American Museum of Natural History, NY, USA for his help in the identification of the scorpions. We would like to thank Sarah Debaveye and Luc Vanden Bosch for technical assistance and Ellen Jorssen for her assistance with the patch clamp experiments on K<INF>v</INF>1.x channels expressed in mammalian cells. TV is research assistant of the Fund for Scientific Research (FWO)-Flanders. IK is a fellow of the Institute for the Promotion of Innovation through Science and Technology (IWT)-Flanders. JT was supported by grants OT/05-064, G.330.06 and G.0257.08 from the Fund for Scientific Research (FWO)-Flanders, and P6/31 (Interuniversity attraction Poles Program - Belgian State - Belgian Science Policy). | - |
dc.language.iso | en | - |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | - |
dc.subject.other | Pharmacology & Pharmacy; Scorpion toxin; Voltage-gated potassium channel; Electrophysiology; Patch clamp; cDNA; Heterometrus laoticus | - |
dc.subject.other | Scorpion toxin; Voltage-gated potassium channel; Electrophysiology; Patch clamp; cDNA; Heterometrus laoticus | - |
dc.title | Purification, molecular cloning and functional characterization of HelaTx1 (Heterometrus laoticus): The first member of a new kappa-KTX subfamily | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 1317 | - |
dc.identifier.issue | 9 | - |
dc.identifier.spage | 1307 | - |
dc.identifier.volume | 83 | - |
local.format.pages | 11 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | Tytgat, J (reprint author),Katholieke Univ Leuven, Toxicol Lab, Onderwijs & Navorsing 2,POB 922,Herestr 49, B-3000 Louvain, Belgium. [Vandendriessche, Thomas; Diego-Garcia, Elia; Abdel-Mottaleb, Yousra; Vermassen, Elke; Tytgat, Jan] Katholieke Univ Leuven, Toxicol Lab, B-3000 Louvain, Belgium. [Kopljar, Ivan; Snyders, Dirk] Univ Antwerp, Lab Mol Biophys Physiol & Pharmacol, B-2610 Antwerp, Belgium. [Jenkins, David Paul; Wulff, Heike] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA. [Clynen, Elke; Schoofs, Liliane] Katholieke Univ Leuven, Res Grp Funct Genom & Prote, B-3000 Louvain, Belgium. [Clynen, Elke] Univ Hasselt, Biomed Res Inst, B-3590 Diepenbeek, Belgium. Jan.Tytgat@pharm.kuleuven.be | - |
local.publisher.place | OXFORD | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.bibliographicCitation.oldjcat | A1 | - |
dc.identifier.doi | 10.1016/j.bcp.2012.01.021 | - |
dc.identifier.isi | 000301906900018 | - |
item.contributor | Vandendriessche, Thomas | - |
item.contributor | Kopljar, Ivan | - |
item.contributor | Jenkins, David Paul | - |
item.contributor | Diego-Garcia, Elia | - |
item.contributor | Abdel-Mottaleb, Yousra | - |
item.contributor | Vermassen, Elke | - |
item.contributor | CLYNEN, Elke | - |
item.contributor | Schoofs, Liliane | - |
item.contributor | Wulff, Heike | - |
item.contributor | Snyders, Dirk | - |
item.contributor | Tytgat, Jan | - |
item.validation | ecoom 2013 | - |
item.fulltext | With Fulltext | - |
item.accessRights | Restricted Access | - |
item.fullcitation | Vandendriessche, Thomas; Kopljar, Ivan; Jenkins, David Paul; Diego-Garcia, Elia; Abdel-Mottaleb, Yousra; Vermassen, Elke; CLYNEN, Elke; Schoofs, Liliane; Wulff, Heike; Snyders, Dirk & Tytgat, Jan (2012) Purification, molecular cloning and functional characterization of HelaTx1 (Heterometrus laoticus): The first member of a new kappa-KTX subfamily. In: BIOCHEMICAL PHARMACOLOGY, 83 (9), p. 1307-1317. | - |
crisitem.journal.issn | 0006-2952 | - |
crisitem.journal.eissn | 1873-2968 | - |
Appears in Collections: | Research publications |
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vandendriessche 1.pdf Restricted Access | Published version | 1.39 MB | Adobe PDF | View/Open Request a copy |
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