Transient species involved in catalytic dioxygen/peroxide activation by hemoproteins: possible involvement of protonated Compound I species.
Interaction of hemoproteins with peroxide leads in several cases to transient formation of ferric peroxo, ferric hydroperoxo, and "high-valent", formally Fev, oxo or hydroxo Compound species. Here, density functional calculations on ferric peroxo, ferric hydroperoxo, Compound and protonated Compound heme active site models are reported. The theoretical results, including calculated isotropic Fermi contact couplings and anisotropic spin dipole couplings, are found to generally correlate well with experimental EPR/ENDOR data. Hydrogen bonding and solvation affect the ferric-peroxo/ferrous-superoxo electromerism. The transition between the two electromers appears smooth, but neither hydrogen bonding to up to two water molecules, nor solvation appear able to dramatically alter the redox state of the superoxo ligand or of the iron. The presence of almost one full unpaired electron on the iron and of one full unpaired electron on the dioxygenic ligand in the "ferric-peroxo" state suggests a possible description of non-protonated "ferric-peroxo" as {ferric-superoxo+porphyrin radical}. Emerging from the DFT data is the possibility that a protonated Compound has already been detected in ENDOR experiments on cytochrome P450. The general feasibility of a protonated Compound in P450 monooxygenases is probed in light of these findings. To encompass the multiple mechanisms available in P450 for substrate oxidation, we define "mechanistic promiscuity" as the feature allowing an enzyme to perform the same reaction, with the same product, using more than one mechanism.
Silaghi-Dumitrescu
Radu
R
Department of Biological Sciences, University of Essex, Colchester, UK. rlsila@essex.ac.uk
Cooper
Chris E
CE
D016880:Anisotropy; D001665:Binding Sites; D002384:Catalysis; D006420:Hemeproteins / Q000737:chemistry* / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism*; D010545:Peroxides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011522:Protons
D006420:Hemeproteins; D010545:Peroxides; D011522:Protons; D010100:Oxygen