Thermally processed Buthus martensii Karsch scorpions are a traditional Chinese medical material for treating various diseases. However, their pharmacological foundation remains unclear. Here, a new degraded peptide of scorpion toxin was identified in Chinese scorpion medicinal material by proteomics. It was named BmK86-P1 and has six conserved cysteine residues. Homology modeling and circular dichroism spectra experiments revealed that BmK86-P1 not only contained representative disulfide bond-stabilized α-helical and β-sheet motifs but also showed remarkable stability at test temperatures from 20–95 °C. Electrophysiology experiments indicated that BmK86-P1 was a highly potent and selective inhibitor of the hKv1.2 channel with IC₅₀ values of 28.5 ± 6.3 nM. Structural and functional dissection revealed that two residues of BmK86-P1 (i.e., Lys¹⁹ and Ile²¹) were the key residues that interacted with the hKv1.2 channel. In addition, channel chimeras and mutagenesis experiments revealed that three amino acids (i.e., Gln³⁵⁷, Val³⁸¹ and Thr³⁸³) of the hKv1.2 channel were responsible for BmK86-P1 selectivity. This research uncovered a new bioactive peptide from traditional Chinese scorpion medicinal material that has desirable thermostability and Kv1.2 channel-specific activity, which strongly suggests that thermally processed scorpions are novel peptide resources for new drug discovery for the Kv1.2 channel-related ataxia and epilepsy diseases.

中文翻译：

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BmK86-P1，一种来自中药蝎子药材的具有理想热稳定性和Kv1.2通道特异性活性的新型降解肽

经热处理的马氏全蝎是治疗各种疾病的中药材。然而，它们的药理基础仍不清楚。在这里，通过蛋白质组学在中药蝎药材中鉴定出一种新的蝎毒素降解肽。它被命名为 BmK86-P1，具有六个保守的半胱氨酸残基。同源建模和圆二色光谱实验表明，BmK86-P1 不仅含有代表性的二硫键稳定的 α-螺旋和 β-折叠基序，而且在 20-95°C 的测试温度下表现出显着的稳定性。电生理学实验表明，BmK86-P1 是一种高效、选择性的 hKv1.2 通道抑制剂，IC ₅₀值为 28.5 ± 6.3 nM。结构和功能剖析显示BmK86-P1 的两个残基（即Lys ¹⁹和Ile ²¹）是与hKv1.2 通道相互作用的关键残基。此外，通道嵌合体和诱变实验表明，三种氨基酸（即 Gln ³⁵⁷、Val ³⁸¹和 Thr ³⁸³) hKv1.2 通道负责 BmK86-P1 选择性。本研究从中药蝎子药材中发现了一种新的生物活性肽，具有良好的热稳定性和Kv1.2通道特异性活性，这强烈表明热处理的蝎子是Kv1.2通道相关性共济失调新药发现的新型肽资源。和癫痫病。