Strassburger W, Wollmer A, Pitts J E, Glover I D, Tickle I J, Blundell T L, Steffens G J, Günzler W A, Otting F, Flohé L
FEBS Lett. 1983 Jul 4;157(2):219-23. doi: 10.1016/0014-5793(83)80551-1.
The sequences of urokinase (UK) and tissue-type plasminogen activator (TPA) were aligned with those of chymotrypsin, trypsin, and elastase according to their 'structurally conserved regions'. In spite of its trypsin-like specificity UK was model-built on the basis of the chymotrypsin structure because of a corresponding disulfide pattern. The extra disulfide bond falls to cysteines 50 and 111d. Insertions can easily be accommodated at the surface. As they occur similarly in both, UK and TPA, a role in plasminogen recognition may be possible. Of the functional positions known to be involved in substrate or inhibitor binding, Asp 97, Lys 143 and Arg 217 (Leu in TPA) may contribute to plasminogen activating specificity. PTI binding may in part be impaired by structural differences at the edge of the binding pocket.
根据尿激酶（UK）和组织型纤溶酶原激活剂（TPA）的“结构保守区域”，将它们的序列与胰凝乳蛋白酶、胰蛋白酶和弹性蛋白酶的序列进行比对。尽管UK具有类胰蛋白酶特异性，但由于其相应的二硫键模式，它是基于胰凝乳蛋白酶的结构构建模型的。额外的二硫键位于半胱氨酸50和111d处。插入物可以很容易地容纳在表面。由于它们在UK和TPA中都类似地出现，因此可能在纤溶酶原识别中起作用。在已知参与底物或抑制剂结合的功能位置中，天冬氨酸97、赖氨酸143和精氨酸217（TPA中为亮氨酸）可能有助于纤溶酶原激活特异性。结合口袋边缘的结构差异可能会部分损害蛋白酶抑制剂（PTI）的结合。
