Sulfoxidation mechanisms catalyzed by cytochrome P450 and horseradish peroxidase models : Spin selection induced by the ligand

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Devesh Kumar
  • Sam P. De Visser
  • Pankaz K. Sharma
  • Hajime Hirao
  • Sason Shaik

Detail(s)

Original languageEnglish
Pages (from-to)8148-8158
Journal / PublicationBiochemistry
Volume44
Issue number22
Publication statusPublished - 7 Jun 2005
Externally publishedYes

Abstract

The sulfoxidation of dimethyl sulfide (DMS), by two different heme-type enzyme models (without the protein), namely, horseradish peroxidase (HRP) and cytochrome P450 (P450), was studied using density functional theory. The models differ from each other by the axial ligand of the iron, which is imidazole in the case of HRP and thiolate in the case of P450. The computational results reveal a concerted oxygen atom transfer to sulfur, with spin-state selection dependent upon the identity of the proximal ligand. In the case of thiolate, the mechanism prefers the high-spin quartet pathway; whereas in the case of imidazole, the mechanism involves two-state reactivity (TSR), with competing quartet and doublet spin states. Furthermore, with thiolate the high-spin transition state, 4TSP450, has an upright conformation with a large Fe-O-SoMs angle of 147°, whereas the low-spin species, 2TSP450, has a small angle and its Fe-O moiety makes an O-NPor bond with one of the nitrogen atoms of the porphine macrocycle. By contrast, when the proximal ligand is imidazole, both transition states possess a bent Fe-O bond and an O-NPor bond. These spin-state selection patterns obey simple orbital selection rules, which are manifestations of the electronic nature of the ligand, i.e., the electron-releasing effect of the thiolate vis-à-vis the electron-withdrawal effect of imidazole. Other possible reactivity expressions of the spin-selection patterns are discussed [Dowers, T. S., Rock, D. A., Rock, D. A., Jones, J. P. (2004) J. Am. Chem. Soc. 126, 8868-8869]. Theory shows that intrinsically, HRP should be as reactive as P450 toward sulfoxidation. © 2005 American Chemical Society.

Citation Format(s)

Sulfoxidation mechanisms catalyzed by cytochrome P450 and horseradish peroxidase models : Spin selection induced by the ligand. / Kumar, Devesh; De Visser, Sam P.; Sharma, Pankaz K.; Hirao, Hajime; Shaik, Sason.

In: Biochemistry, Vol. 44, No. 22, 07.06.2005, p. 8148-8158.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal