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首页> 外文期刊>Biochemistry >Purification, characterization, and synthesis of three novel toxins from the Chinese scorpion Buthus martensi, which act on K+ channels.
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Purification, characterization, and synthesis of three novel toxins from the Chinese scorpion Buthus martensi, which act on K+ channels.

机译：纯化，表征和合成了来自中国蝎子Buthus martensi的三种新型毒素，它们作用于K +通道。

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摘要

Three novel toxins belonging to the scorpion K+ channel-inhibitor family were purified to homogeneity from the venom of B. martensi [Mesobuthus martensi]. They were identified according to their molecular mass (3800-4300 Da) and their neurotoxicityin mice and characterized as 37-amino acid peptides. One of them shows 81-87% sequence identity with members of the kaliotoxin group (named BmKTX), whereas the other two, named BmTX1 and BmTX2, show 65-70% identity with toxins of the charybdotoxin group.Their chemical synthesis by the Fmoc methodology allowed demonstration that BmKTX, unlike BmTX1 and BmTX2, possesses an amidated C-terminal extremity. Toxicity assays in vivo established that they are lethal neurotoxic agents in mice (LD50s of 40-95 ngper mouse). Those toxins proved to be potent inhibitors of the voltage-gated K+ channels, as they were able to compete with [125I]kaliotoxin for its binding to rat brain synaptosomes (IC50s of 0.05-1 nM) and to block the cloned voltage-gated K+ channel Kv1.3 from rat brain, expressed in Xenopus oocytes (IC50s of 0.6-1.6 nM). BmTX1 and BmTX2 were also shown to compete with [125I]charybdotoxin for its binding to the high-conductance Ca2+-activated K+ channels present on bovine aorta sarcolemmal membranes(IC50s of 0.3-0.6 nM). These new sequences show multipoint mutations when compared to the other related scorpion K+ channel toxins and should prove to be useful probes for studying the diverse family of K+ channels.
机译：从马氏芽孢杆菌（Mesobuthus martensi）的毒液中纯化出三种属于蝎K +通道抑制剂家族的新型毒素，使其具有同质性。根据它们的分子量（3800-4300 Da）和它们在小鼠中的神经毒性进行鉴定，并以37个氨基酸的肽为特征。其中之一显示与kaliotoxin组成员（命名为BmKTX）具有81-87％的序列同一性，而另两个命名为BmTX1和BmTX2与charybdotoxin组的毒素具有65-70％的同源性。方法论证明BmKTX与BmTX1和BmTX2不同，它具有酰胺化的C末端末端。体内毒性试验确定它们是小鼠中的致死性神经毒性剂（LD50为40-95 ng /只小鼠）。这些毒素被证明是电压门控K +通道的有效抑制剂，因为它们能够与[125I]碱性毒素竞争与大鼠脑突触体的结合（IC50为0.05-1 nM），并阻断克隆的电压门控K +通道。大鼠大脑中的Kv1.3通道，在非洲爪蟾卵母细胞中表达（IC50为0.6-1.6 nM）。 BmTX1和BmTX2还显示出与[125I]软骨毒素竞争，因为它与存在于牛主动脉肌膜上的高电导Ca2 +激活的K +通道结合（IC50为0.3-0.6 nM）。与其他相关蝎子K +通道毒素相比，这些新序列显示出多点突变，应该被证明是研究K +通道多样化家族的有用探针。

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