Alagon A, Possani L D, Smart J, Schleuning W D
J Exp Med. 1986 Dec 1;164(6):1835-45. doi: 10.1084/jem.164.6.1835.
We have purified and characterized the major N-benzoyl-L-arginine ethyl ester hydrolase from the venom of Heloderma horridum horridum. The enzyme belongs to the serine proteinase family, and its activity vs. peptide amide substrates and human high-molecular-weight kininogen suggests a similarity to the family of kallikreins. This interpretation is corroborated by its reactivity with the natural inhibitors soybean trypsin inhibitor and Kunitz-type bovine pancreatic trypsin inhibitor (aprotinin). Injection of the enzyme (2-16 micrograms/kg) into anesthetized rabbits leads to a rapid dose-dependent transient decrease of the arterial blood pressure. Like glandular kallikrein it specifically converts single-chain tissue type plasminogen activator into its double chain form. In contrast to other kallikrein-like enzymes from snake venoms it shows no thrombin-like or plasminogen activator activity. The enzyme is a single-chain glycoprotein (Mr 63,000). The N-terminal sequence revealed significant homology to pig pancreatic kallikrein and to kallikrein like enzymes from Crotalus atrox and Crotalus adamanteus venom. This enzyme, which we name Helodermatine, is the first purified from Sauria with kallikrein-like properties.
我们已经从珠毒蜥的毒液中纯化并鉴定了主要的N-苯甲酰-L-精氨酸乙酯水解酶。该酶属于丝氨酸蛋白酶家族，其对肽酰胺底物和人高分子量激肽原的活性表明它与激肽释放酶家族相似。大豆胰蛋白酶抑制剂和库尼茨型牛胰蛋白酶抑制剂（抑肽酶）与该酶的反应性证实了这一解释。将该酶（2-16微克/千克）注射到麻醉的兔子体内会导致动脉血压迅速出现剂量依赖性的短暂下降。与腺激肽释放酶一样，它能将单链组织型纤溶酶原激活剂特异性地转化为双链形式。与其他来自蛇毒的激肽释放酶样酶不同，它没有凝血酶样或纤溶酶原激活剂活性。该酶是一种单链糖蛋白（分子量63,000）。其N端序列与猪胰激肽释放酶以及来自西部菱斑响尾蛇和东部菱斑响尾蛇毒液的激肽释放酶样酶具有显著同源性。这种我们命名为珠毒蜥素的酶是首次从有鳞目动物中纯化得到的具有激肽释放酶样特性的酶。
