The intrinsic axial ligand effect on propene oxidation by horseradish peroxidase versus cytochrome P450 enzymes

Devesh Kumar, Sam P. De Visser, Pankaz K. Sharma, Etienne Derat, Sason Shaik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

The axial ligand effect on reactivity of heme enzymes is explored by means of density functional theoretical calculations of the oxidation reactions of propene by a model compound I species of horseradish peroxidase (HRP). The results are assessed vis-à-vis those of cytochrome P450 compound I. It is shown that the two enzymatic species perform C=C epoxidation and C-H hydroxylation in a multistate reactivity scenario with FeIII and FeIV electromeric situations and two different spin states, doublet and quartet. However, while the HRP species preferentially keeps the iron in a low oxidation state (FeIII), the cytochrome P450 species prefers the higher oxidation state (FeIV). It is found that HRP compound I has somewhat lower barriers than those obtained by the cytochrome P450 species. Furthermore, in agreement with experimental observations and studies on model systems, HRP prefers C=C epoxidation, whereas cytochrome P450 prefers C-H hydroxylation. Thus, had the compound I species of HRP been by itself, it would have been an epoxidizing agent, and at least as reactive as cytochrome P450. In the enzyme, HRP is much less reactive than cytochrome P450, presumably because HRP reactivity is limited by the access of the substrate to compound I.

Original languageEnglish
Pages (from-to)181-189
Number of pages9
JournalJournal of Biological Inorganic Chemistry
Volume10
Issue number2
DOIs
StatePublished - Mar 2005

Keywords

  • Cytochrome P450
  • Density functional theory
  • Enzyme catalysis
  • Enzyme models
  • Epoxidation
  • Hydroxylation
  • Peroxidases

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