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How Does Replacement of the Axial Histidine Ligand in Cytochrome c Peroxidase by N(δ)-Methyl Histidine Affect Its Properties and Functions? A Computational Study

Heme peroxidases have important functions in nature related to the detoxification of H(2)O(2). They generally undergo a catalytic cycle where, in the first stage, the iron(III)–heme–H(2)O(2) complex is converted into an iron(IV)–oxo–heme cation radical species called Compound I. Cytochrome c peroxid...

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Detalles Bibliográficos
Autores principales: Lee, Calvin W. Z., Mubarak, M. Qadri E., Green, Anthony P., de Visser, Sam P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583937/
https://www.ncbi.nlm.nih.gov/pubmed/32992593
http://dx.doi.org/10.3390/ijms21197133
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author Lee, Calvin W. Z.
Mubarak, M. Qadri E.
Green, Anthony P.
de Visser, Sam P.
author_facet Lee, Calvin W. Z.
Mubarak, M. Qadri E.
Green, Anthony P.
de Visser, Sam P.
author_sort Lee, Calvin W. Z.
collection PubMed
description Heme peroxidases have important functions in nature related to the detoxification of H(2)O(2). They generally undergo a catalytic cycle where, in the first stage, the iron(III)–heme–H(2)O(2) complex is converted into an iron(IV)–oxo–heme cation radical species called Compound I. Cytochrome c peroxidase Compound I has a unique electronic configuration among heme enzymes where a metal-based biradical is coupled to a protein radical on a nearby Trp residue. Recent work using the engineered N(δ)-methyl histidine-ligated cytochrome c peroxidase highlighted changes in spectroscopic and catalytic properties upon axial ligand substitution. To understand the axial ligand effect on structure and reactivity of peroxidases and their axially N(δ)-methyl histidine engineered forms, we did a computational study. We created active site cluster models of various sizes as mimics of horseradish peroxidase and cytochrome c peroxidase Compound I. Subsequently, we performed density functional theory studies on the structure and reactivity of these complexes with a model substrate (styrene). Thus, the work shows that the N(δ)-methyl histidine group has little effect on the electronic configuration and structure of Compound I and little changes in bond lengths and the same orbital occupation is obtained. However, the N(δ)-methyl histidine modification impacts electron transfer processes due to a change in the reduction potential and thereby influences reactivity patterns for oxygen atom transfer. As such, the substitution of the axial histidine by N(δ)-methyl histidine in peroxidases slows down oxygen atom transfer to substrates and makes Compound I a weaker oxidant. These studies are in line with experimental work on N(δ)-methyl histidine-ligated cytochrome c peroxidases and highlight how the hydrogen bonding network in the second coordination sphere has a major impact on the function and properties of the enzyme.
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spelling pubmed-75839372020-10-29 How Does Replacement of the Axial Histidine Ligand in Cytochrome c Peroxidase by N(δ)-Methyl Histidine Affect Its Properties and Functions? A Computational Study Lee, Calvin W. Z. Mubarak, M. Qadri E. Green, Anthony P. de Visser, Sam P. Int J Mol Sci Article Heme peroxidases have important functions in nature related to the detoxification of H(2)O(2). They generally undergo a catalytic cycle where, in the first stage, the iron(III)–heme–H(2)O(2) complex is converted into an iron(IV)–oxo–heme cation radical species called Compound I. Cytochrome c peroxidase Compound I has a unique electronic configuration among heme enzymes where a metal-based biradical is coupled to a protein radical on a nearby Trp residue. Recent work using the engineered N(δ)-methyl histidine-ligated cytochrome c peroxidase highlighted changes in spectroscopic and catalytic properties upon axial ligand substitution. To understand the axial ligand effect on structure and reactivity of peroxidases and their axially N(δ)-methyl histidine engineered forms, we did a computational study. We created active site cluster models of various sizes as mimics of horseradish peroxidase and cytochrome c peroxidase Compound I. Subsequently, we performed density functional theory studies on the structure and reactivity of these complexes with a model substrate (styrene). Thus, the work shows that the N(δ)-methyl histidine group has little effect on the electronic configuration and structure of Compound I and little changes in bond lengths and the same orbital occupation is obtained. However, the N(δ)-methyl histidine modification impacts electron transfer processes due to a change in the reduction potential and thereby influences reactivity patterns for oxygen atom transfer. As such, the substitution of the axial histidine by N(δ)-methyl histidine in peroxidases slows down oxygen atom transfer to substrates and makes Compound I a weaker oxidant. These studies are in line with experimental work on N(δ)-methyl histidine-ligated cytochrome c peroxidases and highlight how the hydrogen bonding network in the second coordination sphere has a major impact on the function and properties of the enzyme. MDPI 2020-09-27 /pmc/articles/PMC7583937/ /pubmed/32992593 http://dx.doi.org/10.3390/ijms21197133 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
Lee, Calvin W. Z.
Mubarak, M. Qadri E.
Green, Anthony P.
de Visser, Sam P.
How Does Replacement of the Axial Histidine Ligand in Cytochrome c Peroxidase by N(δ)-Methyl Histidine Affect Its Properties and Functions? A Computational Study
title How Does Replacement of the Axial Histidine Ligand in Cytochrome c Peroxidase by N(δ)-Methyl Histidine Affect Its Properties and Functions? A Computational Study
title_full How Does Replacement of the Axial Histidine Ligand in Cytochrome c Peroxidase by N(δ)-Methyl Histidine Affect Its Properties and Functions? A Computational Study
title_fullStr How Does Replacement of the Axial Histidine Ligand in Cytochrome c Peroxidase by N(δ)-Methyl Histidine Affect Its Properties and Functions? A Computational Study
title_full_unstemmed How Does Replacement of the Axial Histidine Ligand in Cytochrome c Peroxidase by N(δ)-Methyl Histidine Affect Its Properties and Functions? A Computational Study
title_short How Does Replacement of the Axial Histidine Ligand in Cytochrome c Peroxidase by N(δ)-Methyl Histidine Affect Its Properties and Functions? A Computational Study
title_sort how does replacement of the axial histidine ligand in cytochrome c peroxidase by n(δ)-methyl histidine affect its properties and functions? a computational study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583937/
https://www.ncbi.nlm.nih.gov/pubmed/32992593
http://dx.doi.org/10.3390/ijms21197133
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