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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7583937 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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