尿激酶
丝氨酸蛋白酶
苯甲脒
纤溶酶原激活剂
化学
尿激酶受体
突变体
激活剂(遗传学)
立体化学
丝氨酸
晶体结构
生物物理学
结晶学
蛋白酶
生物化学
酶
生物
受体
基因
内分泌学
遗传学
作者
Ewa Żesławska,Andrea Schweinitz,Annette Kärcher,Peter Sondermann,Stefan Sperl,Jörg Stürzebecher,Uwe Jacob
标识
DOI:10.1006/jmbi.2000.3966
摘要
Urokinase is a serine protease involved in cancer growth and metastasis. Here we present the first urokinase crystal structure in complex with reversible inhibitors at 2.1 and 2.6 Å resolution. These inhibitor complex structures have been obtained from crystals of engineered urokinase type plasminogen activator designed to obtain a crystal form open for inhibitor soaking. The mutant C122S loses its flexible A-chain upon activation cleavage and crystallises in the presence of benzamidine, which was later displaced by the desired inhibitor. This new soakable crystal form turned out to be of great value in the process of structure-based drug design. The evaluated binding mode of amiloride, and UKI-1D revealed a new subsite of the primary specificity pocket of urokinase that will be employed in the future ligand optimisation process.
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