PAI-1 is the primary physiologic inhibitor of urokinase-type plasminogen activator （uPA） and tissue-type plasminogen activator （tPA） and plays important roles in a number of physiologic processes including fibrinolysis, angiogenesis, wound healing, and cell migration. PAI-1 has been proposed as a potential target for inhibitor development and many inhibitors have been reported. However, little was known about the inhibitory mechanism of these inhibitors. Here we determine the crystal structure of PAI-1 in complex with a reported inhibitor, sodium gallate. The PAI-1 ：gallate structure shows that gallate inserts into the cavity formed by helix D, helix E, helix F and t-strand 2A. This work provides insights into the inhibitory mechanism of gallate and lays out structural basis for further PAI-I inhibitor design.
Human blood coagulation factor XI （FXI） is a key enzyme in the amplification phase of blood coagulation cascade, and is recognized as an important target for anti-coagulant development in recent years. We designed a new mutant form of FXIa catalytic domain rhFXI370-607 （N73Q-N113Q-C123S）, and report here the facile preparation, protein crystallization, and crystal structure of this protein. We highlight a few unique structural features of FXIa after comparison with the trypsin family serine proteases at sequence and structural levels. This work provides a foundation to develop new small molecular FXIa inhibitors with increased potency and specificity.
