Solution structure of IsTX. A male scorpion toxin from Opisthacanthus madagascariensis (Ischnuridae)

European Journal of Biochemistry
Nahoko YamajiTakashi Iwashita

Abstract

The novel sex-specific potassium channel inhibitor IsTX, a 41-residue peptide, was isolated from the venom of male Opisthacanthus madagascariensis. Two-dimensional NMR techniques revealed that the structure of IsTX contains a cysteine-stabilized alpha/beta-fold. IsTX is classified, based on its sequential and structural similarity, in the scorpion short toxin family alpha-KTx6. The alpha-KTx6 family contains a single alpha-helix and two beta-strands connected by four disulfide bridges and binds to voltage-gated K(+) channels and apamin-sensitive Ca(2+)-activated K(+) channels. The three-dimensional structure of IsTX is similar to that of Heterometrus spinifer toxin (HsTX1). HsTX1 blocks the Kv1.3 channel at picomolar concentrations, whereas IsTX has much lower affinities (10 000-fold). To investigate the structure-activity relationship, the geometry of sidechains and electrostatic surface potential maps were compared with HsTX1. As a result of the comparison of the primary structures, Lys27 of IsTX was conserved at the same position in HsTX1. The analogous Lys23 of HsTX1, the most critical residue for binding to potassium channels, binds to the channel pore. However, IsTX has fewer basic residues to interact with acidic channel...Continue Reading

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Citations

Jul 16, 2013·The Journal of Venomous Animals and Toxins Including Tropical Diseases·Rodolfo Rodríguez-RaveloLourival D Possani
Dec 8, 2009·Bioscience, Biotechnology, and Biochemistry·Nobuto MatsushitaHisashi Miyagawa
Dec 1, 2006·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Terumi Nakajima
Apr 22, 2009·Toxicon : Official Journal of the International Society on Toxinology·Edelyn C N SilvaElisabeth F Schwartz
Nov 28, 2016·Toxicon : Official Journal of the International Society on Toxinology·Jimena Isaias Cid UribeLourival Domingos Possani
Oct 13, 2006·Toxicon : Official Journal of the International Society on Toxinology·Elisabeth F SchwartzLourival D Possani

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