Wang X, Terzyan S, Tang J, Loy J A, Lin X, Zhang X C
Oklahoma Medical Research Foundation, Crystallography Program, 825 N. E. 13(th) Street, Oklahoma City, OK, 73104, USA.
J Mol Biol. 2000 Jan 28;295(4):903-14. doi: 10.1006/jmbi.1999.3397.
Activation of the serine protease plasmin from its zymogen, plasminogen, is the key step in fibrinolysis leading to blood clot dissolution. It also plays critical roles in cell migration, such as in tumor metastasis. Here, we report the crystal structure of an inactive S741A mutant of human plasminogen catalytic domain at 2.0 A resolution. This structure permits a direct comparison with that of the plasmin catalytic unit. Unique conformational differences are present between these two structures that are not seen in other zymogen-enzyme pairs of the trypsin family. The functional significance of these differences and the structural basis of plasminogen activation is discussed in the light of this new structure.
丝氨酸蛋白酶纤溶酶从其酶原纤溶酶原的激活是导致血凝块溶解的纤维蛋白溶解的关键步骤。它在细胞迁移中也起着关键作用，例如在肿瘤转移中。在这里，我们报告了人纤溶酶原催化结构域的无活性S741A突变体在2.0埃分辨率下的晶体结构。该结构允许与纤溶酶催化单元的结构进行直接比较。这两种结构之间存在独特的构象差异，而在胰蛋白酶家族的其他酶原-酶对中未见这种差异。根据这一新结构讨论了这些差异的功能意义和纤溶酶原激活的结构基础。
