Human coagulation Factor V（FV）, together with Factor Xa, assembles to prothrombinase complex on activated cell surface, which converts prothrombin into thrombin, leading to fibrin deposition. The C2 domain of FV is believed to be a primary anchor for the assembly of pro- thrombinase on the cell surface, and was proposed as a target to intervene with pathological thrombotic events. We report here the crystal structure of the C2 domain of FV fused to maltose-binding protein（MBP）. The fusion tag of MBP is critical to generate the crystal for this study. There is no strong interaction between MBP and FVC2. The overall structure of FVC2 is similar to the previous FVC2 structures, suggesting the MBP fusion does not perturb the molecular structure of FVC2. This crystal form of FVC2 can be used for future study of molecular interaction between FVC2 and its inhibitors.
As a trypsin-like serine protease, Urokinase-type plasminogen activator （uPA） plays a key role in a range of biological processes including plasminogen activation, angiogenesis, wound healing, tissue remodeling, tumor growth and tumor metastasis, uPA is shown as the most validated marker for prognosis of breast cancer. Inhibitors of uPA may then be useful in the treatment of cancer by retarding tumor growth and metastasis. Most current uPA inhibitors employ a highly basic group （amidine or guanidine group） to target the primary specific pocket of uPA active site, which leads to poor oral bioavailability. Here, a uPA inhibitor with weak basic P1 group, 2-（2-amino- benzothiazole-6-carboxamido）acetic acid （ABTCA）, was synthesized and reported here. In addition, we also determined the crystal structure of ABTCA in complex with uPA. The structural information will be useful for further improvements of potency and selectivity of this promising new type ofuPA inhibitors.
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.
