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Gewählte Publikation:

Stampler, J; Bellei, M; Soudi, M; Gruber, C; Battistuzzi, G; Furtmüller, PG; Obinger, C; .
(2011): Manipulating the proximal triad His-Asn-Arg in human myeloperoxidase.
Arch Biochem Biophys. 2011; 516(1):21-28 FullText FullText_BOKU

In mammalian peroxidases the proximal histidine is in close interaction with a fully conserved asparagine which in turn is hydrogen bonded with an arginine that stabilizes the propionate substituent of pyrrol ring Din bent conformation. In order to probe the role of this rigid proximal architecture for structural integrity and catalysis of human myeloperoxidase (MPO), the variants Asn421Asp, Arg333Ala and Arg333Lys have been recombinantly expressed in HEK cell lines. The standard reduction potential of the Fe(III)/Fe(II) couple of Asn421Asp was still wild-type-like (-50 mV at pH 7.0) but the spectral properties of the ferric and ferrous forms as well as of higher oxidation states showed significant differences. Additionally, rates of ligand binding and oxidation of both one- and two-electron donors were diminished. The effect of exchange of Arg333 was even more dramatic. We did not succeed in production of mutant proteins that could bind heme at the active site. The importance of this His-Asn-Arg triad in linking the heme iron with the propionate at pyrrol ring D for heme insertion and binding as well as in maintenance of the architecture of the substrate binding site(s) at the entrance to the heme cavity is discussed. (C) 2011 Elsevier Inc. All rights reserved.
Autor*innen der BOKU Wien:
Furtmüller Paul Georg
Grünwald-Gruber Clemens
Obinger Christian
Soudi Monika
Stampler Johanna Maria
Find related publications in this database (using NML MeSH Indexing)
Amino Acid Substitution;Arginine/chemistry;Arginine/genetics;Arginine/metabolism;Asparagine/chemistry;Asparagine/genetics;Asparagine/metabolism;Binding Sites;Cell Line;Cloning, Molecular;Ferric Compounds/metabolism;Ferrous Compounds/metabolism;Heme/metabolism*;Histidine/chemistry;Histidine/genetics;Histidine/metabolism;Humans;Models, Molecular;Mutant Proteins/chemistry;Mutant Proteins/genetics;Mutant Proteins/metabolism;Oxidation-Reduction;Peroxidase/chemistry*;Peroxidase/genetics;Peroxidase/metabolism*;

Find related publications in this database (Keywords)
Proximal histidine
Redox thermodynamics
Heme modification
Heme distortion
Halide oxidation
Innate immune system

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