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Mechanism of the Dinuclear Iron Enzyme p ‐Aminobenzoate N‐oxygenase from Density Functional Calculations
Author(s) -
Wei WenJie,
Siegbahn Per E. M.,
Liao RongZhen
Publication year - 2019
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201801072
Subject(s) - chemistry , molecule , bond cleavage , peroxide , ligand (biochemistry) , photochemistry , stereochemistry , reaction mechanism , substrate (aquarium) , density functional theory , reaction intermediate , electron paramagnetic resonance , redox , catalysis , computational chemistry , inorganic chemistry , organic chemistry , biochemistry , oceanography , receptor , geology , physics , nuclear magnetic resonance
AurF is a diiron enzyme that utilizes two dioxygen molecules as the oxidant to catalyze the oxidation of p ‐aminobenzoate to p ‐nitrobenzoate. Density functional calculations were performed to elucidate the reaction mechanism of this enzyme. Two different models were considered, with the oxygenated intermediate being a diferric peroxo species or a diferric hydroperoxo species. The calculations strongly favor the model with a diferric peroxo species and support the mechanism proposed by Bollinger and co‐workers. The reaction starts with the binding of a dioxygen molecule to the diferrous center to generate a diferric peroxide complex. This is followed by the cleavage of the O−O bond, concertedly with the formation of the first N−O bond, which has a barrier of only 9.2 kcal/mol. Subsequently, the first‐shell ligand Glu227 abstracts a proton from the substrate. After the delivery of two electrons from the external reductant and two protons from solution, a water molecule and the experimentally suggested intermediate p ‐hydroxylaminobenzoate are produced and the diferrous center is regenerated. The oxidation of the p ‐hydroxylaminobenzoate intermediate requires the binding of a second dioxygen molecule to the diferrous center to generate the diferric peroxide complex. Similarly to the oxidation of p ‐aminobenzoate, the O−O bond cleavage and the formation of the second N−O bond take place in a concerted step. The p ‐nitrobenzoate product is formed after the release of two protons and two electrons from the substrate. The model with a hydroperoxo species gave a much high barrier of 28.7 kcal/mol for the substrate oxidation due to the large energy penalty for the generation of the active hydroperoxo species.