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

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 unwan...

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Autores principales: Dayer, Mohammad Reza, Ghayour, Omid, Dayer, Mohammad Saaid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scholarly Research Network 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320014/
https://www.ncbi.nlm.nih.gov/pubmed/22536522
http://dx.doi.org/10.5402/2012/762728
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author Dayer, Mohammad Reza
Ghayour, Omid
Dayer, Mohammad Saaid
author_facet Dayer, Mohammad Reza
Ghayour, Omid
Dayer, Mohammad Saaid
author_sort Dayer, Mohammad Reza
collection PubMed
description 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.
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spelling pubmed-33200142012-04-25 Mechanism of Protein-Z-Mediated Inhibition of Coagulation Factor Xa by Z-Protein-Dependent Inhibitor: A Molecular Dynamic Approach Dayer, Mohammad Reza Ghayour, Omid Dayer, Mohammad Saaid ISRN Hematol Research Article 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. International Scholarly Research Network 2012-03-20 /pmc/articles/PMC3320014/ /pubmed/22536522 http://dx.doi.org/10.5402/2012/762728 Text en Copyright © 2012 Mohammad Reza Dayer et al. https://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Research Article
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
title Mechanism of Protein-Z-Mediated Inhibition of Coagulation Factor Xa by Z-Protein-Dependent Inhibitor: A Molecular Dynamic Approach
title_full Mechanism of Protein-Z-Mediated Inhibition of Coagulation Factor Xa by Z-Protein-Dependent Inhibitor: A Molecular Dynamic Approach
title_fullStr Mechanism of Protein-Z-Mediated Inhibition of Coagulation Factor Xa by Z-Protein-Dependent Inhibitor: A Molecular Dynamic Approach
title_full_unstemmed Mechanism of Protein-Z-Mediated Inhibition of Coagulation Factor Xa by Z-Protein-Dependent Inhibitor: A Molecular Dynamic Approach
title_short Mechanism of Protein-Z-Mediated Inhibition of Coagulation Factor Xa by Z-Protein-Dependent Inhibitor: A Molecular Dynamic Approach
title_sort mechanism of protein-z-mediated inhibition of coagulation factor xa by z-protein-dependent inhibitor: a molecular dynamic approach
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320014/
https://www.ncbi.nlm.nih.gov/pubmed/22536522
http://dx.doi.org/10.5402/2012/762728
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