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The Structure of Blood Coagulation Factor XIII Is Adapted to Oxidation

The blood coagulation factor XIII (FXIII) plays a critical role in supporting coagulation and fibrinolysis due to both the covalent crosslinking of fibrin polymers, rendering them resistant to plasmin lysis, and the crosslinking of fibrin to proteins of the fibrinolytic system. The hypochlorite-medi...

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Autores principales: Vasilyeva, Alexandra, Yurina, Lyubov, Shchegolikhin, Alexander, Indeykina, Maria, Bugrova, Anna, Kononikhin, Alexey, Nikolaev, Eugene, Rosenfeld, Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355775/
https://www.ncbi.nlm.nih.gov/pubmed/32560304
http://dx.doi.org/10.3390/biom10060914
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author Vasilyeva, Alexandra
Yurina, Lyubov
Shchegolikhin, Alexander
Indeykina, Maria
Bugrova, Anna
Kononikhin, Alexey
Nikolaev, Eugene
Rosenfeld, Mark
author_facet Vasilyeva, Alexandra
Yurina, Lyubov
Shchegolikhin, Alexander
Indeykina, Maria
Bugrova, Anna
Kononikhin, Alexey
Nikolaev, Eugene
Rosenfeld, Mark
author_sort Vasilyeva, Alexandra
collection PubMed
description The blood coagulation factor XIII (FXIII) plays a critical role in supporting coagulation and fibrinolysis due to both the covalent crosslinking of fibrin polymers, rendering them resistant to plasmin lysis, and the crosslinking of fibrin to proteins of the fibrinolytic system. The hypochlorite-mediated oxidation of the blood coagulation factor XIII (FXIII) at the different stages of its enzymatic activation is studied for the first time in this paper. The consolidated results obtained with the aid of MS/MS, electrophoresis, and colorimetry demonstrate that in the process of FXIII’s conversion into FXIIIa, the vulnerability of FXIII to hypochlorite-induced oxidation increased as follows: native FXIII < FXIII + Ca(2+) << FXIII + Ca(2+)/thrombin. The modification sites were detected among all the structural regions of the catalytic FXIII-A subunit, except for the activation peptide, and embraced several sushi domains of the FXIII-B subunit. Oxidized amino acid residues belonging to FXIII-A are surface-exposed residues and can perform an antioxidant role. The regulatory FXIII-B subunits additionally contribute to the antioxidant defense of the catalytic center of the FXIII-A subunits. Taken together, the present data along with the data from previous studies demonstrate that the FXIII proenzyme structure is adapted to oxidation.
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spelling pubmed-73557752020-07-23 The Structure of Blood Coagulation Factor XIII Is Adapted to Oxidation Vasilyeva, Alexandra Yurina, Lyubov Shchegolikhin, Alexander Indeykina, Maria Bugrova, Anna Kononikhin, Alexey Nikolaev, Eugene Rosenfeld, Mark Biomolecules Article The blood coagulation factor XIII (FXIII) plays a critical role in supporting coagulation and fibrinolysis due to both the covalent crosslinking of fibrin polymers, rendering them resistant to plasmin lysis, and the crosslinking of fibrin to proteins of the fibrinolytic system. The hypochlorite-mediated oxidation of the blood coagulation factor XIII (FXIII) at the different stages of its enzymatic activation is studied for the first time in this paper. The consolidated results obtained with the aid of MS/MS, electrophoresis, and colorimetry demonstrate that in the process of FXIII’s conversion into FXIIIa, the vulnerability of FXIII to hypochlorite-induced oxidation increased as follows: native FXIII < FXIII + Ca(2+) << FXIII + Ca(2+)/thrombin. The modification sites were detected among all the structural regions of the catalytic FXIII-A subunit, except for the activation peptide, and embraced several sushi domains of the FXIII-B subunit. Oxidized amino acid residues belonging to FXIII-A are surface-exposed residues and can perform an antioxidant role. The regulatory FXIII-B subunits additionally contribute to the antioxidant defense of the catalytic center of the FXIII-A subunits. Taken together, the present data along with the data from previous studies demonstrate that the FXIII proenzyme structure is adapted to oxidation. MDPI 2020-06-17 /pmc/articles/PMC7355775/ /pubmed/32560304 http://dx.doi.org/10.3390/biom10060914 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vasilyeva, Alexandra
Yurina, Lyubov
Shchegolikhin, Alexander
Indeykina, Maria
Bugrova, Anna
Kononikhin, Alexey
Nikolaev, Eugene
Rosenfeld, Mark
The Structure of Blood Coagulation Factor XIII Is Adapted to Oxidation
title The Structure of Blood Coagulation Factor XIII Is Adapted to Oxidation
title_full The Structure of Blood Coagulation Factor XIII Is Adapted to Oxidation
title_fullStr The Structure of Blood Coagulation Factor XIII Is Adapted to Oxidation
title_full_unstemmed The Structure of Blood Coagulation Factor XIII Is Adapted to Oxidation
title_short The Structure of Blood Coagulation Factor XIII Is Adapted to Oxidation
title_sort structure of blood coagulation factor xiii is adapted to oxidation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355775/
https://www.ncbi.nlm.nih.gov/pubmed/32560304
http://dx.doi.org/10.3390/biom10060914
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