BmK86-P1, a New Degradation Peptide with Desirable Thermostability and Kv1.2 Channel-Specific Activity from Traditional Chinese Scorpion Medicinal Material.
BmK86-P1, a New Degradation Peptide with Desirable Thermostability and Kv1.2 Channel-Specific Activity from Traditional Chinese Scorpion Medicinal Material.
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BmK86-P1，一种来自中药全蝎的新型降解肽，具有良好的热稳定性和 Kv1.2 通道特异性活性
DOI：
10.3390/toxins13090610
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发表时间：
2021-08-30
期刊：
影响因子：
4.2
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Qin C;Yang X;Zuo Z;Yang L;Yang F;Cao Z;Chen Z;Wu Y
经热处理的马氏蝎子是一种治疗多种疾病的中药材。然而，它们的药理学基础仍不清楚。本研究通过蛋白质组学方法在中药蝎子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 hKv1.2 通道的高效选择性抑制剂，IC50 值为 28.5 ± 6.3 nM。结构和功能解剖表明，BmK86-P1 的两个残基（即 Lys19 和 Ile21）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，hKv1.2通道的三个氨基酸（即Gln357、Val381和Thr383）负责BmK86-P1选择性。本研究从传统中药蝎子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，这有力地表明，热处理后的蝎子是用于治疗Kv1.2通道相关共济失调和癫痫疾病的新药开发的新型肽资源。
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.
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影响因子：
11.2
作者：
Helbig, Katherine L.;Hedrich, Ulrike B. S.;Shinde, Deepali N.;Krey, Ilona;Teichmann, Anne-Christin;Hentschel, Julia;Schubert, Julian;Chamberlin, Adam C.;Huether, Robert;Lu, Hsiao-Mei;Alcaraz, Wendy A.;Tang, Sha;Jungbluth, Chelsy;Dugan, Sarah L.;Vainionpaa, Leena;Karle, Kathrin N.;Synofzik, Matthis;Schols, Ludger;Schule, Rebecca;Lehesjoki, Anna-Elina;Helbig, Ingo;Lerche, Holger;Lemke, Johannes R.
通讯作者：
Lemke, Johannes R.
影响因子：
9.9
作者：
Corbett, Mark A.;Bellows, Susannah T.;Gecz, Jozef
通讯作者：
Gecz, Jozef
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DOI：
10.1016/j.bbrc.2014.01.094
发表时间：
2014-02-14
影响因子：
3.1
作者：
Xie, Chang;Li, Tian;Wu, Yingliang
通讯作者：
Wu, Yingliang
影响因子：
3.1
作者：
Hundallah, Khaled;Alenizi, Asma'a;Tabarki, Brahim
通讯作者：
Tabarki, Brahim
蝎子重组α毒素BmKM9的表达及其钠通道功能表征
影响因子：
3
作者：
Yang, Fan;Liu, Shuang;Wu, Yingliang
通讯作者：
Wu, Yingliang