BOKU - Universität für Bodenkultur Wien - Forschungsinformationssystem
Gewählte Publikation:
Paumann-Page, M; Furtmüller, PG; Hofbauer, S; Paton, LN; Obinger, C; Kettle, AJ; .
(2013):
Inactivation of human myeloperoxidase by hydrogen peroxide.
Arch Biochem Biophys. 2013; 539(1):51-62
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- Abstract:
- Human myeloperoxidase (MPO) uses hydrogen peroxide generated by the oxidative burst of neutrophils to produce an array of antimicrobial oxidants. During this process MPO is irreversibly inactivated. This study focused on the unknown role of hydrogen peroxide in this process. When treated with low concentrations of H2O2 in the absence of reducing substrates, there was a rapid loss of up to 35% of its peroxidase activity. Inactivation is proposed to occur via oxidation reactions of Compound I with the prosthetic group or amino acid residues. At higher concentrations hydrogen peroxide acts as a suicide substrate with a rate constant of inactivation of 3.9 x 10(-3) s(-1). Treatment of MPO with high H2O2 concentrations resulted in complete inactivation, Compound III formation, destruction of the heme groups, release of their iron, and. detachment of the small polypeptide chain of MPO. Ten of the protein's methionine residues were oxidized and the thermal stability of the protein decreased. Inactivation by high concentrations of H2O2 is proposed to occur via the generation of reactive oxidants when H2O2 reacts with Compound III. These mechanisms of inactivation may occur inside neutrophil phagosomes when reducing substrates for MPO become limiting and could be exploited when designing pharmacological inhibitors. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
- Autor*innen der BOKU Wien:
- Furtmüller Paul Georg
- Hofbauer Stefan
- Obinger Christian
- Paumann-Page Martina
- Find related publications in this database (using NML MeSH Indexing)
- Enzyme Activation/drug effects;Enzyme Stability/drug effects;Heme/chemistry;Heme/metabolism;Humans;Hydrogen Peroxide/pharmacology*;Kinetics;Peroxidase/antagonists & inhibitors;Peroxidase/chemistry*;Peroxidase/metabolism*;Protein Structure, Secondary/drug effects;Protein Structure, Tertiary/drug effects;Protein Subunits/chemistry;Protein Subunits/metabolism;Protein Unfolding/drug effects;Temperature;
- Find related publications in this database (Keywords)
- Myeloperoxidase
- Neutrophils
- Oxidative stress
- Suicide inhibitor
- Mechanism-based inhibition
- Oxidative modification
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