Investigation and biochemical study of novel neurotoxins and thrombo-toxin from the venoms of Elapidae and Viperidae snakes.

眼镜蛇和蝰蛇毒液中新型神经毒素和血栓毒素的调查和生化研究。

• 批准号: 12575035
• 负责人: MORITA Takashi
• 金额: $ 7.87万
• 依托单位: MEIJI PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12575035/
• 关键词: neurotoxin; thrombo-toxin; C-type lectin-like protein; Elapidae snake; Viperidae snake; コブラ科蛇毒

Snake venom contains a diverse range of interesting proteins, including procoagulants, anticoagulants, fibrinolytic components, platelet agonists, platelet antagonists, and hemorrhagic components. One of the functional components of snake venom is a member of the C-type lectin-like protein (CLP) family that includes factor IX/X-binding protein (IX-X-bp), carinactivase-1 (calcium-dependent prothrombin activator), RVV-X (factor X activator of Russell's viper venom), alboaggregin-B (platelet agonist), and flavocetin-A (platelet antagonist). These CLPs perform a variety of activities, and various CLPs have been sequenced. CLPs have proved to be useful tools in elucidating the complex mechanisms involved in clotting and platelet formation and the structure-function relationship of human clotting factors and glycoproteins of platelets.We isolated, characterized, and cloned genes for three novel CRISP family proteins (piscivorin, ophanin, and catrin) from the venom of eastern cottonmouth (Agkislrodon piscivorus piscivorus), king cobra (Ophiophagus hannah), and western diamondback rattlesnake (Crotalus atrox). Our results show the wide distribution of snake venom CRISP family proteins among Viperidae and Elapidae from different continents, indicating that CRISP family proteins compose a new group of snake venom proteins.

蛇毒含有多种有趣的蛋白质，包括促凝剂、抗凝剂、纤溶成分、血小板激动剂、血小板拮抗剂和出血成分。蛇毒的功能成分之一是C型凝集素样蛋白(CLP)家族的成员之一，该家族包括凝血因子IX/X结合蛋白(IX-X-BP)、钙依赖凝血酶原激活剂(Carin激活酶-1)、RVV-X(罗素蛇毒的凝血因子X激活剂)、白聚集素-B(血小板激动剂)和黄素-A(血小板拮抗剂)。这些CLP执行各种活动，并且已经对各种CLP进行了排序。我们从东方棉口蛇(Agkislrodon Pisciorus Pisciorus)、眼镜王蛇(Ophiphagus Hannah)和西部响尾蛇(Crotalus Atrox)的毒液中分离、鉴定和克隆了三个新的脆性家族蛋白基因(Pisciorin、ophanin和Catrin)。我们的结果表明，蛇毒脆性家族蛋白在不同大陆的蛇科和眼镜蛇科中分布广泛，表明脆性家族蛋白构成了一组新的蛇毒蛋白。

项目成果

奥田 大樹ら: "Purification and characterization of a new RGD/KGD-containing dimeric disintegrin, piscivostatin, from the venom of Agkistrodon piscivorus piscivorus: The unique effect of piscivostatin on platelet aggregation."J.Biochem.. 130. 403-415 (2001)

Daiki Okuda 等人：“从 Agkistrodon piscivorus piscivorus 的毒液中纯化和表征一种新的含有 RGD/KGD 的二聚解整合素 piscivostatin：piscivostatin 对血小板聚集的独特作用。”J.Biochem.. 130. 403- 415（2001）

Okuda D., Nozaki C., Sekiya F., Morita T.: "Comparative biochemistry of disintegrins isolated from snake venom : Consideration of the taxonomy and geographical distribution of the snakes in the genus Echis."J.Biochem.. 129. 516-620 (2001)

Okuda D.、Nozaki C.、Sekiya F.、Morita T.：“从蛇毒中分离出的解整合素的比较生物化学：考虑 Echis 属蛇的分类学和地理分布。”J.Biochem.. 129. 516

Okuda D., Koike H., Morita T.: "A new gene structure of the disintegrin family : A subunit of dimeric disintegrin has short coding region."Biochemistry. 41. 14248-14254 (2002)

Okuda D.、Koike H.、Morita T.：“解整合素家族的新基因结构：二聚解整合素的亚基具有短编码区。”生物化学。

山崎 泰男ら: "Snake venom vascular endothelial growth factors (VEGFs) exhibit potent activity through their specific recognition of KDR VEGF receptor 2)."J.Biol.Chem.. 278(5). 51985-51988 (2003)

Yasuo Yamazaki 等人：“蛇毒血管内皮生长因子 (VEGF) 通过特异性识别 KDR VEGF 受体 2) 表现出强大的活性。J.Biol.Chem.. 278(5) (2003)。

Mizuno H., Fujimoto Z., Atoda H., Morita T.: "Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X."Proc.Natl.Acad.Sci.USA. 98. 7230-7234 (2001)

Mizuno H.、Fujimoto Z.、Atoda H.、Morita T.：“与 X 因子 Gla 结构域复合的抗凝血蛋白的晶体结构。”Proc.Natl.Acad.Sci.USA。