Ma Hakim, Xiao-Peng Tang, Yang Shi-Long, Lu Qiu-Min, Lai Ren
Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of sciences, Kunming 650223, China; Graduate University of Chinese Academy of Sciences, Beijing 100009, China.
Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of sciences, Kunming 650223, China; Joint Laboratory of Natural peptide, University of Science and Technology of China and Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Chin J Nat Med. 2016 Aug;14(8):607-14. doi: 10.1016/S1875-5364(16)30071-1.
It is hypothesized that protease inhibitors play an essential role in survival of venomous animals through protecting peptide/protein toxins from degradation by proteases in their prey or predators. However, the biological function of protease inhibitors in scorpion venoms remains unknown. In the present study, a trypsin inhibitor was purified and characterized from the venom of scorpion Mesobuthus eupeus, which enhanced the biological activities of crude venom components in mice when injected in combination with crude venom. This protease inhibitor, named MeKTT-1, belonged to Kunitz-type toxins subfamily. Native MeKTT-1 selectively inhibited trypsin with a Kivalue of 130 nmol·L(-1). Furthermore, MeKTT-1 was shown to be a thermo-stable peptide. In animal behavioral tests, MeKTT-1 prolonged the pain behavior induced by scorpion crude venom, suggesting that protease inhibitors in scorpion venom inhibited proteases and protect the functionally important peptide/protein toxins from degradation, consequently keeping them active longer. In conclusion, this was the first experimental evidence about the natural existence of serine protease inhibitor in the venom of scorpion Mesobuthus eupeus, which preserved the activity of venom components, suggests that scorpions may use protease inhibitors for survival.
据推测，蛋白酶抑制剂在有毒动物的生存中起着至关重要的作用，它能保护肽/蛋白质毒素不被猎物或捕食者体内的蛋白酶降解。然而，蝎子毒液中蛋白酶抑制剂的生物学功能仍不清楚。在本研究中，从东亚钳蝎毒液中纯化并鉴定出一种胰蛋白酶抑制剂，当与粗毒液联合注射时，它能增强粗毒液成分在小鼠体内的生物活性。这种蛋白酶抑制剂名为MeKTT-1，属于库尼茨型毒素亚家族。天然MeKTT-1对胰蛋白酶具有选择性抑制作用，其Ki值为130 nmol·L(-1)。此外，MeKTT-1是一种热稳定肽。在动物行为测试中，MeKTT-1延长了蝎子粗毒液诱导的疼痛行为，这表明蝎子毒液中的蛋白酶抑制剂抑制了蛋白酶，保护了功能重要的肽/蛋白质毒素不被降解，从而使它们的活性保持更长时间。总之，这是关于东亚钳蝎毒液中天然存在丝氨酸蛋白酶抑制剂的首个实验证据，它能保留毒液成分的活性，表明蝎子可能利用蛋白酶抑制剂来生存。
