title: Non-heme Fe(IV)-oxo intermediates.
abstract: High-valent non-heme iron-oxo intermediates have been proposed for decades as the key intermediates in numerous biological oxidation reactions. In the past three years, the first direct characterization of such intermediates has been provided by studies of several alphaKG-dependent oxygenases that catalyze either hydroxylation or halogenation of their substrates. In each case, the Fe(IV)-oxo intermediate is implicated in cleavage of the aliphatic C-H bond to initiate hydroxylation or halogenation. The observation of non-heme Fe(IV)-oxo intermediates and Fe(II)-containing product(s) complexes with almost identical spectroscopic parameters in the reactions of two distantly related alphaKG-dependent hydroxylases suggests that members of this subfamily follow a conserved mechanism for substrate hydroxylation. In contrast, for the alphaKG-dependent non-heme iron halogenase, CytC3, two distinct Fe(IV) complexes form and decay together, suggesting that they are in rapid equilibrium. The existence of two distinct conformers of the Fe site may be the key factor accounting for the divergence of the halogenase reaction from the more usual hydroxylation pathway after C-H bond cleavage. Distinct transformations catalyzed by other mononuclear non-heme enzymes are likely also to involve initial C-H bond cleavage by Fe(IV)-oxo complexes, followed by diverging reactivities of the resulting Fe(III)-hydroxo/substrate radical intermediates.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. ckrebs@psu.edu
authors.forename: Carsten
authors.initials: C
authors.lastname: Krebs
authors.forename: Danica
authors.initials: D
authors.lastname: Galonić Fujimori
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Walsh
authors.forename: J Martin
authors.initials: JM
authors.lastname: Bollinger
mesh_terms: D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D003574:Cytochrome c Group / Q000737:chemistry / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D006900:Hydroxylation; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000378:metabolism; D010105:Oxygenases / Q000737:chemistry*; D047090:beta-Lactams / Q000737:chemistry / Q000378:metabolism
chemical_list: D003574:Cytochrome c Group; D005290:Ferric Compounds; D047090:beta-Lactams; C066317:ferryl iron; C017165:cytochrome c(3); D007501:Iron; D006899:Mixed Function Oxygenases; D010105:Oxygenases; C433064:taurine-alpha-ketoglutarate dioxygenase