Proton assisted oxygen-oxygen bond splitting in cytochrome p450

A.R. Groenhof, A.W. Ehlers, K. Lammertsma

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Proton assisted O-O bond splitting of cytochromes' P450 hydroperoxo Compound O has been investigated by density functional theory, showing a barrier for the slightly endothermic formation of the iron-oxo Compound I. The barrier and the endothermicity increase with decreasing acidity of the distal proton source. Protonation of the proximal iron heme ligand favors the O-O bond scission and provides an important regulatory component in the catalytic cycle. The Compound 0 → 1 conversion is slightly exothermic for the peroxidase and catalase models. Implications of the energetic relationship between the two reactive intermediates are discussed in terms of possible oxidative pathways. © 2007 American Chemical Society.
Original languageEnglish
Pages (from-to)6204-9
JournalJournal of the American Chemical Society
Volume129
Issue number19
DOIs
Publication statusPublished - 2007

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Cytochrome P-450 Enzyme System
Protons
Iron
Oxygen
Protonation
Heme
Acidity
Catalase
Peroxidase
Density functional theory
Ligands

Cite this

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title = "Proton assisted oxygen-oxygen bond splitting in cytochrome p450",
abstract = "Proton assisted O-O bond splitting of cytochromes' P450 hydroperoxo Compound O has been investigated by density functional theory, showing a barrier for the slightly endothermic formation of the iron-oxo Compound I. The barrier and the endothermicity increase with decreasing acidity of the distal proton source. Protonation of the proximal iron heme ligand favors the O-O bond scission and provides an important regulatory component in the catalytic cycle. The Compound 0 → 1 conversion is slightly exothermic for the peroxidase and catalase models. Implications of the energetic relationship between the two reactive intermediates are discussed in terms of possible oxidative pathways. {\circledC} 2007 American Chemical Society.",
author = "A.R. Groenhof and A.W. Ehlers and K. Lammertsma",
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pages = "6204--9",
journal = "Journal of the American Chemical Society",
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Proton assisted oxygen-oxygen bond splitting in cytochrome p450. / Groenhof, A.R.; Ehlers, A.W.; Lammertsma, K.

In: Journal of the American Chemical Society, Vol. 129, No. 19, 2007, p. 6204-9.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Proton assisted oxygen-oxygen bond splitting in cytochrome p450

AU - Groenhof, A.R.

AU - Ehlers, A.W.

AU - Lammertsma, K.

PY - 2007

Y1 - 2007

N2 - Proton assisted O-O bond splitting of cytochromes' P450 hydroperoxo Compound O has been investigated by density functional theory, showing a barrier for the slightly endothermic formation of the iron-oxo Compound I. The barrier and the endothermicity increase with decreasing acidity of the distal proton source. Protonation of the proximal iron heme ligand favors the O-O bond scission and provides an important regulatory component in the catalytic cycle. The Compound 0 → 1 conversion is slightly exothermic for the peroxidase and catalase models. Implications of the energetic relationship between the two reactive intermediates are discussed in terms of possible oxidative pathways. © 2007 American Chemical Society.

AB - Proton assisted O-O bond splitting of cytochromes' P450 hydroperoxo Compound O has been investigated by density functional theory, showing a barrier for the slightly endothermic formation of the iron-oxo Compound I. The barrier and the endothermicity increase with decreasing acidity of the distal proton source. Protonation of the proximal iron heme ligand favors the O-O bond scission and provides an important regulatory component in the catalytic cycle. The Compound 0 → 1 conversion is slightly exothermic for the peroxidase and catalase models. Implications of the energetic relationship between the two reactive intermediates are discussed in terms of possible oxidative pathways. © 2007 American Chemical Society.

U2 - 10.1021/ja0685654

DO - 10.1021/ja0685654

M3 - Article

VL - 129

SP - 6204

EP - 6209

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 19

ER -