Ferric superoxide and ferric hydroxide are used in the catalytic mechanism of hydroxyethylphosphonate dioxygenase: a density functional theory investigation.
Hydroxyethylphosphonate dioxygenase (HEPD) is a mononuclear nonheme iron enzyme that utilizes an O(2) molecule to cleave a C-C bond in 2-hydroxyethylphosphonate and produce hydroxymethylphosphonate (HMP) and formic acid. Density functional theory calculations were performed on an enzyme active-site model of HEPD to understand its catalytic mechanism. The reaction starts with H-abstraction from the C2 position of 2-HEP by a ferric superoxide-type (Fe(III)-OO(•-)) intermediate, in a similar manner to the H-abstraction in the reaction of the dinuclear iron enzyme myo-inositol oxygenase. The resultant Fe(II)-OOH intermediate may follow either a hydroperoxylation or hydroxylation pathway, the former process being energetically more favorable. In the hydroperoxylation pathway, a ferrous-alkylhydroperoxo intermediate is formed, and then its O-O bond is homolytically cleaved to yield a complex of ferric hydroxide with a gem-diol radical. Subsequent C-C bond cleavage within the gem-diol leads to formation of an R-CH(2)(•) species and one of the two products (i.e., formic acid). The R-CH(2)(•) then intramolecularly forms a C-O bond with the ferric hydroxide to provide the other product, HMP. The overall reaction pathway does not require the use of a high-valent ferryl intermediate but does require ferric superoxide and ferric hydroxide intermediates.
Fukui Institute for Fundamental Chemistry, Kyoto University, 34-4 Takano Nishihiraki-cho, Sakyo, Kyoto 606-8103, Japan.
Hajime
H
Hirao
Keiji
K
Morokuma
D002384:Catalysis; D020134:Catalytic Domain; D049308:Dioxygenases / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry*; D008954:Models, Biological; D015394:Molecular Structure; D063065:Organophosphonates / Q000737:chemistry*; D011789:Quantum Theory; D013481:Superoxides / Q000737:chemistry*
C519566:2-hydroxyethyl phosphonate; D005290:Ferric Compounds; D063065:Organophosphonates; D013481:Superoxides; C021024:ferric hydroxide; D049308:Dioxygenases