Mechanism of Protein-Z-Mediated Inhibition of Coagulation Factor Xa by Z-Protein-Dependent Inhibitor : A Molecular Dynamic Approach
Joint Authors
Dayer, Mohammad Saaid
Dayer, Mohammad Reza
Ghayour, Omid
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-03-20
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Dayer, Mohammad Reza& Ghayour, Omid& Dayer, Mohammad Saaid. 2012. Mechanism of Protein-Z-Mediated Inhibition of Coagulation Factor Xa by Z-Protein-Dependent Inhibitor : A Molecular Dynamic Approach. ISRN Hematology،Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-496814
Modern Language Association (MLA)
Dayer, Mohammad Reza…[et al.]. Mechanism of Protein-Z-Mediated Inhibition of Coagulation Factor Xa by Z-Protein-Dependent Inhibitor : A Molecular Dynamic Approach. ISRN Hematology No. 2012 (2012), pp.1-8.
https://search.emarefa.net/detail/BIM-496814
American Medical Association (AMA)
Dayer, Mohammad Reza& Ghayour, Omid& Dayer, Mohammad Saaid. Mechanism of Protein-Z-Mediated Inhibition of Coagulation Factor Xa by Z-Protein-Dependent Inhibitor : A Molecular Dynamic Approach. ISRN Hematology. 2012. Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-496814
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-496814