Multiple mechanisms of cytochrome P450-catalyzed substrate hydroxylations |
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Authors: | David C. Heimbrook Stephen G. Sligar |
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Affiliation: | Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511 USA |
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Abstract: | We have examined the 5--hydroxylation of camphor by cytochrome P450 in [18O] water/buffer solution. In the reaction of the reconstituted multienzyme system, no 18O-label is observed in the product alcohol. Similarly, in the m-chloroperbenzoic acid or cumene hydroperoxide supported reactions with ferric P450, solvent oxygen is not incorporated into hydroxycamphor. When the analagous reaction is carried out using iodosobenzene as the exogenous oxidant, however, the alcoholic oxygen of the product is derived entirely from the solvent. These results cannot be explained by equilibration of the iodosobenzene oxygen with solvent water before reacting with P450, and suggest a unique mechanism for iodosobenzene-supported P450 oxygenations. We propose two distinct mechanistic activities for cytochrome P450: a hydroxylase, and an oxene transferase, with the former encompassing the classic oxygenase as well as “peroxygenase” reactions. |
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Keywords: | PhIO iodosobenzene PhI iodobenzene m-CPBA m-chloroperbenzoic acid FT-IR Fourier transform infrared spectroscopy mass ion |
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