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Title: kappa-Hefutoxin1, a novel toxin from the scorpion Heterometrus fulvipes with unique structure and function. Importance of the functional diad in potassium channel selectivity
Authors: Srinivasan, Kellathur N ×
Sivaraja, Vaithiyalingam
Huys, Isabelle
Sasaki, Toru
Cheng, Betty
Kumar, Thallampuranam Krishnaswamy S
Sato, Kazuki
Tytgat, Jan
Yu, Chin
San, B Chia Cheng
Ranganathan, Shoba
Bowie, H John
Kini, R Manjunatha
Gopalakrishnakone, Ponnampalam #
Issue Date: Aug-2002
Publisher: Amer soc biochemistry molecular biology inc
Series Title: Journal of Biological Chemistry vol:277 issue:33 pages:30040-7
Abstract: An important and exciting challenge in the postgenomic era is to understand the functions of newly discovered proteins based on their structures. The main thrust is to find the common structural motifs that contribute to specific functions. Using this premise, here we report the purification, solution NMR, and functional characterization of a novel class of weak potassium channel toxins from the venom of the scorpion Heterometrus fulvipes. These toxins, kappa-hefutoxin1 and kappa-hefutoxin2, exhibit no homology to any known toxins. NMR studies indicate that kappa-hefutoxin1 adopts a unique three-dimensional fold of two parallel helices linked by two disulfide bridges without any beta-sheets. Based on the presence of the functional diad (Tyr(5)/Lys(19)) at a distance (6.0 +/- 1.0 A) comparable with other potassium channel toxins, we hypothesized its function as a potassium channel toxin. kappa-Hefutoxin 1 not only blocks the voltage-gated K(+)-channels, Kv1.3 and Kv1.2, but also slows the activation kinetics of Kv1.3 currents, a novel feature of kappa-hefutoxin 1, unlike other scorpion toxins, which are considered solely pore blockers. Alanine mutants (Y5A, K19A, and Y5A/K19A) failed to block the channels, indicating the importance of the functional diad.
URI: 
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Toxicology and Pharmacology
Research Centre for Pharmaceutical Care and Pharmaco-economics (-)
Research Unit KU Leuven Centre for IT & IP Law (CiTiP)
× corresponding author
# (joint) last author

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