44 / 2021-10-09 21:32:08

Study on the Fibrinolytic Activity and Molecular Docking with Plasminogen of FGFC1

Keywords: FGFC1; pro-uPA; plasminogen; molecular docking; fibrinolytic activity characteristics

Abstract: The objective of this study is to further evaluate the fibrinolytic activity characterization of FGFC1 mediated by plasminogen (Glu-/Lys-) and a single-chain urokinase-type plasminogen activator (pro-uPA). The fibrinolytic activity characteristics of FGFC1 mediated by Pro-uPA, Glu-/lys-plasminogen, EACA (6-aminohexanoic acid) and TXA (tranexamic acid) were investigated by constructing fibrinolytic system containng Glu-/ Lys-plasminogen and Pro-uPA in vitro, and the docking site and mode of FGFC1 with plasminogen were explored by molecular docking. The absorbance of the mixture was measured at 405 nm using a microplate reader at 37 ℃, and reaction rate was calculated according to the time-absorbance curve. The results showed that a relatively low concentration of FGFC1 enhances fibrinolytic activity. Compared with Glu-plasminogen, the fibrinolytic activity mediated by Lys-plasminogen was stronger when the concentration of FGFC1 was below 0.048 mM. In addition, EACA, TXA and SBTI (Soybean Trypsin Inhibitor) remarkably inhibited the fibrinolytic activity of FGFC1. The molecular docking results showed that both EACA and FGFC1 were bound to five kringle domains (KR1–KR5) of plasminogen with moderately high affinity. FGFC1 was conjugated to plasminogen with a binding affinity of − 8.0 kcal/moL. These data show that the mechanism of the interaction between FGFC1 and Glu-plasminogen may be related to its conversion to Lys-plasminogen and the lysine-binding sites (LBSs) play a crucial role in the process of FGFC1 binding to plasminogen. This study provides a theoretical basis for the clinical pharmacology of FGFC1 and a reference for the development of novel plasminogen activators.