Table of Contents
ISRN Hematology
Volume 2012, Article ID 762728, 8 pages
Research Article

Mechanism of Protein-Z-Mediated Inhibition of Coagulation Factor Xa by Z-Protein-Dependent Inhibitor: A Molecular Dynamic Approach

1Department of Biology, Faculty of Science, Shahid Chamran University, Ahvaz 6198864936, Iran
2Department of Mathematics, Faculty of Mathematical and Computer Sciences, Shahid Chamran University, Ahvaz, Iran
3Department of Parasitology and Medical Entomology, Tarbiat Modares University, Tehran, Iran

Received 14 November 2011; Accepted 10 January 2012

Academic Editor: C. H. Lawrie

Copyright © 2012 Mohammad Reza Dayer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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-fold. Inhibition of coagulation cascade via FXa by ZPI and other serpins is very important safety factor for normal homeostasis protecting human life against unwanted thrombosis. In the present work using native structure of PZ, ZPI, FXa and in a dynamic simulation, using NAMD software, the ternary complex was studied in an up to 10 nanoseconds protocol. Rely on trajectory analyses, we postulated that PZ binds ZPI by using its SP-like domain and through noncovalent forces. PZ then transfers ZPI through-out the blood, and by using its GLA domain and a bivalent cation of calcium, PZ binds to phospholipid bilayers (e.g., platelet) where the FXa is preallocated. In case of PZ-ZPI binding to plasma membrane, a series of complementary interactions take place between FXa, and PZ-ZPI complex including interactions between RCL loop of ZPI and catalytic site of FXa and some take place between long arm of PZ (composed of GLA, EGF1, and EGF2 domains) and GLA domain of FXa. In our claim these complementary interactions lead PZ to bind correctly to prelocated FXa.