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Formation of the Iron–Oxo Hydroxylating Species in the Catalytic Cycle of Aromatic Amino Acid Hydroxylases
Author(s) -
Olsson Elaine,
Martinez Aurora,
Teigen Knut,
Jensen Vidar R.
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201002910
Subject(s) - chemistry , hexacoordinate , catalytic cycle , pterin , catalysis , stereochemistry , cofactor , tetrahydrobiopterin , bond cleavage , crystallography , ligand (biochemistry) , oxidoreductase , phenylalanine hydroxylase , amino acid , photochemistry , medicinal chemistry , phenylalanine , enzyme , organic chemistry , biochemistry , receptor , silicon
The first part of the catalytic cycle of the pterin‐dependent, dioxygen‐using nonheme‐iron aromatic amino acid hydroxylases, leading to the Fe IV O hydroxylating intermediate, has been investigated by means of density functional theory. The starting structure in the present investigation is the water‐free FeO 2 complex cluster model that represents the catalytically competent form of the enzymes. A model for this structure was obtained in a previous study of water‐ligand dissociation from the hexacoordinate model complex of the X‐ray crystal structure of the catalytic domain of phenylalanine hydroxylase in complex with the cofactor (6 R )‐ L ‐ erythro ‐5,6,7,8‐tetrahydrobiopterin (BH 4 ) (PAH‐Fe II ‐BH 4 ). The OO bond rupture and two‐electron oxidation of the cofactor are found to take place via a Fe‐O‐O‐BH 4 bridge structure that is formed in consecutive radical reactions involving a superoxide ion, O 2 − . The overall effective free‐energy barrier to formation of the Fe IV O species is calculated to be 13.9 kcal mol −1 , less than 2 kcal mol −1 lower than that derived from experiment. The rate‐limiting step is associated with a one‐electron transfer from the cofactor to dioxygen, whereas the spin inversion needed to arrive at the quintet state in which the OO bond cleavage is finalized, essentially proceeds without activation.