Protein Z is a plasma protein functioning as a carrier for ZPI. Protein Z also accelerates inhibitory effect of ZPI on factor Xa by 1000-\r\nfold. Inhibition of coagulation cascade via FXa by ZPI and other serpins is very important safety factor for normal homeostasis\r\nprotecting human life against unwanted thrombosis. In the present work using native structure of PZ, ZPI, FXa and in a dynamic\r\nsimulation, using NAMD software, the ternary complex was studied in an up to 10 nanoseconds protocol. Rely on trajectory\r\nanalyses, we postulated that PZ binds ZPI by using its SP-like domain and through noncovalent forces. PZ then transfers ZPI\r\nthrough-out the blood, and by using its GLA domain and a bivalent cation of calcium, PZ binds to phospholipid bilayers (e.g.,\r\nplatelet) where the FXa is preallocated. In case of PZ-ZPI binding to plasma membrane, a series of complementary interactions\r\ntake place between FXa, and PZ-ZPI complex including interactions between RCL loop of ZPI and catalytic site of FXa and some\r\ntake place between long arm of PZ (composed of GLA, EGF1, and EGF2 domains) and GLA domain of FXa. In our claim these\r\ncomplementary interactions lead PZ to bind correctly to prelocated FXa.
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