Structural insights into the activation of blood coagulation factor XI zymogen by thrombin: A computational molecular dynamics study

In this study, we employed a combination of molecular docking and microsecond time-scale molecular dynamics simulations to identify the key regions of interaction between fXI and thrombin. The activating complex between the substrate and enzyme was modeled to represent the initial acylation step of the serine-protease hydrolysis mechanism. The proposed solution structural complex, fIX:fIIa, obtained from 3 microseconds of MD refinement, suggests that the activation of factor XI is mediated by thrombin's anion binding exosite-II interactions with A3 and A4 domains. We predict that the two positively charged arginine residues (Arg409 and Arg413) in the exosite-2 region, the β- and γ-insertion loops of thrombin play an important structural role in the initial activating complex between fXI and thrombin.PMID:34923393 | DOI:10.1016/j.bpc.2021.106737

Source: Biophysical Chemistry - December 19, 2021 Category: Chemistry Authors: Shenna Shearin Divi Venkateswarlu Source Type: research