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Open AccessArticle

The Structure of Blood Coagulation Factor XIII Is Adapted to Oxidation

1
N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia
2
V.L. Talrose Institute for Energy Problems of Chemical Physics, N.N. Semenov Federal Center of Chemical Physics, Russian Academy of Sciences, Chernogolovka, 142432 Moscow, Russia
3
Moscow Institute of Physics and Technology (State University), Dolgoprudny, 141701 Moscow, Russia
4
Skolkovo Institute of Science and Technology, 121205 Moscow, Russia
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(6), 914; https://doi.org/10.3390/biom10060914
Received: 26 April 2020 / Revised: 11 June 2020 / Accepted: 16 June 2020 / Published: 17 June 2020
(This article belongs to the Section Biochemistry)
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 + Ca2+ << FXIII + Ca2+/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. View Full-Text
Keywords: blood coagulation factor XIII (FXIII); hypochlorite-induced oxidation; oxidative modifications; reactive oxygen species (ROS); HPLC-MS/MS; structural adaptation blood coagulation factor XIII (FXIII); hypochlorite-induced oxidation; oxidative modifications; reactive oxygen species (ROS); HPLC-MS/MS; structural adaptation
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    Doi: 10.5281/zenodo.3766614
    Link: https://doi.org/10.5281/zenodo.3766614
    Description: THE STRUCTURE OF BLOOD COAGULATION FACTOR XIII IS ADAPTED TO OXIDATION (supplementary files) Figure S1. The presentation of the catalytic FXIII-subunit dimer crystal structure (PDB ID: 1F13) with the oxidative modifications detected in the oxidized samples. Table S1. The list of identified peptides containing oxidatively modified residues in the FXIII subunits. Table S2. Export data on peptides and modifications found by Peaks Studio 8.5.
MDPI and ACS Style

Vasilyeva, A.; Yurina, L.; Shchegolikhin, A.; Indeykina, M.; Bugrova, A.; Kononikhin, A.; Nikolaev, E.; Rosenfeld, M. The Structure of Blood Coagulation Factor XIII Is Adapted to Oxidation. Biomolecules 2020, 10, 914.

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