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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Scholarly Research Network
2012
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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. |
format | Online Article Text |
id | pubmed-3320014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | International Scholarly Research Network |
record_format | MEDLINE/PubMed |
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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