Plasminogen activator inhibitor-1 polymers, induced by inactivating amphipathic organochemical ligands.
Plasminogen activator inhibitor-1 polymers, induced by inactivating amphipathic organochemical ligands.
复制标题
纤溶酶原激活剂抑制剂-1 聚合物，通过灭活两亲性有机化学配体诱导。
作者：
Katrine Pedersen;A. P. Einholm;A. Christensen;L. Schack;T. Wind;J. Kenney;P. Andreasen
纤溶酶原激活物抑制剂-1（派-1）的抗蛋白水解活性的带负电荷的有机化学灭活剂将其转化为无活性的聚合物。如通过天然凝胶电泳所研究的，派-1聚合物的大小范围从大于20个单位的二聚体到多聚体。与天然派-1相比，聚合物表现出对温度诱导的解折叠的增加的抗性。聚合与非靶蛋白酶消化模式的特定变化相关。在与尿激酶型纤溶酶原激活剂孵育期间，聚合物缓慢转化为反应性中心裂解的单体，表明聚合物中末端派-1分子的底物行为。派-1的四重突变体与延迟率的潜伏期转换也有延迟率的聚合。研究了一些丝氨酸蛋白酶抑制剂的天然凝胶电泳，配体诱导的聚合只观察到派-1和肝素辅因子II，这也能够共聚。基于这些结果，我们认为派-1特定区域中配体的结合导致所谓的环片聚合，其中一个分子的反应中心环与另一个分子中的β片A结合。小的有机化学配体的丝氨酸蛋白酶抑制剂聚合的诱导是一个新的发现，是蛋白质化学的兴趣，在一般的病理蛋白质聚合。
Negatively charged organochemical inactivators of the anti-proteolytic activity of plasminogen activator inhibitor-1 (PAI-1) convert it to inactive polymers. As investigated by native gel electrophoresis, the size of the PAI-1 polymers ranged from dimers to multimers of more than 20 units. As compared with native PAI-1, the polymers exhibited an increased resistance to temperature-induced unfolding. Polymerization was associated with specific changes in patterns of digestion with non-target proteases. During incubation with urokinase-type plasminogen activator, the polymers were slowly converted to reactive centre-cleaved monomers, indicating substrate behaviour of the terminal PAI-1 molecules in the polymers. A quadruple mutant of PAI-1 with a retarded rate of latency transition also had a retarded rate of polymerization. Studying a number of serpins by native gel electrophoresis, ligand-induced polymerization was observed only with PAI-1 and heparin cofactor II, which were also able to copolymerize. On the basis of these results, we suggest that the binding of ligands in a specific region of PAI-1 leads to so-called loop-sheet polymerization, in which the reactive centre loop of one molecule binds to beta-sheet A in another molecule. Induction of serpin polymerization by small organochemical ligands is a novel finding and is of protein chemical interest in relation to pathological protein polymerization in general.
影响因子：
2.9
作者：
MAST, AE;ENGHILD, JJ;SALVESEN, G
通讯作者：
SALVESEN, G