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Autocatalytic nitration of P450cam peroxynitrite

Item Type:Article
Title:Autocatalytic nitration of P450cam peroxynitrite
Creators Name:Daiber, A. and Schoeneich, C. and Schmidt, P. and Jung, C. and Ullrich, V.
Abstract:Peroxynitrite (PN) gains high selectivity as a physiological oxidizing and nitrating agent through catalysis by metal ions. This was established for the heme-thiolate (P450) enzyme prostacyclin synthase which was tyrosine nitrated and inhibited at low PN levels [FEBS Lett. 382 (1996) 101]. Other P450 proteins reacted in a similar manner and a ferryl species (Compound II) has been identified as an intermediate during reactions with PN [Nitric Oxide 3 (1999) 142]. Here we investigated cytochrome P450(CAM) and found that it catalyzes the decomposition of PN as well as an increased nitration of phenol. The latter at the expense of phenol hydroxylation is characteristic for the proton-assisted PN action. PN also caused self-nitration of P450(CAM) at several tyrosine residues. Two of them, Y 96 and Y 305 were largely protected in the presence of the ligand metyrapone. Unlike other heme-thiolate proteins P450(CAM) did not form distinct spectral intermediates characteristic for Compound II. We conclude that P450(CAM) serves as a model for the nitration of prostacyclin synthase with respect to its autocatalytic tyrosine nitration and its prevention by blocking the active site.
Keywords:Compound II, Metal-Catalysis, Nitration, P450 Enzymes, Peroxynitrite
Source:Journal of Inorganic Biochemistry
Page Range:213-220
Date:31 August 2000
Official Publication:https://doi.org/10.1016/S0162-0134(00)00110-0
PubMed:View item in PubMed

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