Structural and Functional Studies of Plasmin Inhibitors

Human plasmin is a plasma serine protease that plays key roles in fibrinolysis, wound healing and cell migration. Accordingly, anti-fibrinolytics targeting plasmin have been widely used for treating life-threatening bleeding during surgeries or in trauma. However, current plasmin-targeting drugs are limited by poor potency or low specificity. Our researcher here characterized the functions and structures of different plasmin specific inhibitors and illustrated the inhibition mechanisms mainly via X-ray crystallography. This work revealed distinct structural features of plasmin active-site within the serine protease family, and developed highly selective plasmin inhibitors, which rationalizes structure-aided drug design and future clinical studies.