The proliferation of toxic organisms caused by changes in the marine environment, coupled with the rising human activities along the coastal lines, has resulted in an increasing number of stinging incidents, posing a serious threat to public health. Here, we evaluated the systemic toxicity of the venom in jellyfish at both cellular and animal levels, and found that jellyfish tentacle extract (TE) has strong lethality accompanied by abnormal elevation of blood biochemical indicators and pathological changes. Joint analysis of transcriptome and proteome indicated that metalloproteinases are the predominant toxins in jellyfish. Specially, two key metalloproteinases DN6695_c0_g3 and DN8184_c0_g7 were identified by mass spectrometry of the red blood cell membrane and tetracycline hydrochloride (Tch) inhibition models. Structurally, molecular docking and kinetic analysis are employed and observed that Tch could inhibit the enzyme activity by binding to the hydrophobic pocket of the catalytic center. In this study, we demonstrated that Tch impedes the metalloproteinase activity thereby reducing the lethal effect of jellyfish, which suggests a potential strategy for combating the health threat of marine toxic jellyfish.

中文翻译：

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海洋危险水母金属蛋白酶的发现和干预的见解


海洋环境变化导致有毒生物大量繁殖，加上人类沿海活动增多，蜇伤事件不断增多，对公众健康构成严重威胁。在此，我们从细胞和动物水平评估了水母毒液的全身毒性，发现水母触手提取物（TE）具有很强的杀伤力，并伴有血液生化指标异常升高和病理变化。转录组和蛋白质组的联合分析表明金属蛋白酶是水母中的主要毒素。特别是，通过红细胞膜和盐酸四环素 (Tch) 抑制模型的质谱分析鉴定了两种关键金属蛋白酶 DN6695_c0_g3 和 DN8184_c0_g7。在结构上，采用分子对接和动力学分析，观察到Tch可以通过与催化中心的疏水性口袋结合来抑制酶活性。在这项研究中，我们证明 Tch 会阻碍金属蛋白酶活性，从而减少水母的致死作用，这提出了对抗海洋有毒水母健康威胁的潜在策略。