tailieunhanh - Báo cáo khoa học: Solution structure of IsTX A male scorpion toxin fromOpisthacanthus madagascariensis(Ischnuridae)

The novel sex-specific potassium channel inhibitor IsTX, a 41-residue peptide, was isolated from the venom of male Opisthacanthus techniques revealed that the structure of IsTX contains a cysteine-stabilizeda/b-fold. IsTX is classified, based on its sequential and structural similarity, in the scorpion short toxin familya-KTx6. Thea-KTx6 family contains a single a-helix and twob-strands connected by four disulfide brid-ges and binds to voltage-gated K + channels and apamin-sensitive Ca 2+ -activated K + channels. . | Eur. J. Biochem. 271 3855-3864 2004 FEBS 2004 doi Solution structure of IsTX A male scorpion toxin from Opisthacanthus madagascariensis Ischnuridae Nahoko Yamaii1. Li Dai1 Kenji Suaase1 Marta Andriantsiferana2 Terumi Nakaiima1 and Takashi Iwashita1 1Suntory Institute for Bioorganic Research Mishima-Gun Osaka Japan 2Faculty of Science University of Antananarivo Madagascar 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 a b-fold. IsTX is classified based on its sequential and structural similarity in the scorpion short toxin family a-KTx6. The a-KTx6 family contains a single a-helix and two b-strands connected by four disulfide bridges and binds to voltage-gated K channels and apamin-sensitive Ca2 -activated K channels. The three-dimensional structure of IsTX is similar to that of Heterometrus spinifer toxin HsTX1 . HsTX1 blocks the 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 surfaces than HsTX1. MALDI-TOF MS analysis clearly indicated that IsTX was found in male scorpion venom but not in female. This is the first report that scorpion venom contains sex-specific compounds. Keywords cysteine-stabilized a b-fold NMR potassium channels scorpion toxin sex-specific toxin. The venom of Opisthacanthus nutdagascariensis scorpions from the Ischnuridae family .

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