南京大学学报（自然科学版）2005，Vol.41Issue(5)：478-488,11.
Kunitz抑制剂家族成员抑肽酶对纤溶酶原活化的抑制作用
Inhibition of Plasminogen Activation by a Kunitz Inhibitor, Aprotinin
王莹 1孙自勇 1刘建宁1
作者信息
- 1. 南京大学分子医学研究所,南京大学,南京,210093
- 折叠
摘要
Abstract
Aprotinin, a natural inhibitor belonging to the Kunitz family, is known to inhibit proteolysis of kallikrein, plasmin and trypsin. In the present study, aprotinin was shown to inhibit plasminogen activation by urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA). By contrast,the amidolytic activities of these activators against their synthetic substrates were not inhibited by aprotinin.The mechanism of action was investigated using u-PA, and it was shown that aprotinin bound specifically to u-PA but not to plasminogen. Since aprotinin was also found to bind to low molecular weight u-PA, the binding site was therefore concluded to be the protease domain. However, it did not directly block the active site of u-PA, since the u-PA activity against the synthetic substrate was preserved. The findings suggested a model of action which has not been previously described for either Kunitz inhibitors or plasminogen activator inhibitors.Since the structure of aprotinin closely resembles certain human Kunitz inhibitors, these studies prompted the hypothesis that the pathway of plasminogen activation in vivo may not be soldy under the control of serpins, as is currently believed.关键词
抑肽酶/丝氨酸蛋白酶/Kunitz抑制剂/抑制作用/尿激酶型纤溶酶原激活剂/组织型纤溶酶原激活剂Key words
aprotinin/serine protease/Kunitz inhibitor/inhibition/urokinase-type plasminogen activator/tissue-type plasminogen activator分类
生物科学引用本文复制引用
王莹,孙自勇,刘建宁..Kunitz抑制剂家族成员抑肽酶对纤溶酶原活化的抑制作用[J].南京大学学报（自然科学版）,2005,41(5):478-488,11.
