1hp9
kappa-Hefutoxins: a novel Class of Potassium Channel Toxins from Scorpion venom
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OverviewOverview
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.
About this StructureAbout this Structure
1HP9 is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
ReferenceReference
kappa-Hefutoxin1, a novel toxin from the scorpion Heterometrus fulvipes with unique structure and function. Importance of the functional diad in potassium channel selectivity., Srinivasan KN, Sivaraja V, Huys I, Sasaki T, Cheng B, Kumar TK, Sato K, Tytgat J, Yu C, San BC, Ranganathan S, Bowie HJ, Kini RM, Gopalakrishnakone P, J Biol Chem. 2002 Aug 16;277(33):30040-7. Epub 2002 May 28. PMID:12034709
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