Binding modes of prothrombin cleavage site sequences to the factor Xa catalytic triad: Insights from atomistic simulations.

ABSTRACT: Prothrombin is a key zymogen of the coagulation process and can be converted to thrombin by the prothrombinase complex, which consists of factor Xa (FXa), cofactor Va (FVa), and phospholipids. Prothrombin can be activated at two cleavage sites, R271 and R320, which generates two intermediates: prethrombin-2 via the initial cleavage at R271, and meizothrombin via the first cleavage at R320. Several mechanisms have been proposed to explain this activation preference, but the role of cleavage site sequences in prothrombin activation has not been thoroughly investigated. Here, we used an advanced sampling technique, parallel tempering metadynamics with a well-tempered ensemble (PTMetaD-WTE), to study the binding modes of prothrombin cleavage site sequences R²⁶⁶AIEGRTATSEY²⁷⁷

SUBMITTER: Li J 

PROVIDER: S-EPMC9529552 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature