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Water Dissociation and Dioxygen Binding in Phenylalanine Hydroxylase
Author(s) -
Olsson Elaine,
Martinez Aurora,
Teigen Knut,
Jensen Vidar R.
Publication year - 2010
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.200900489
Subject(s) - chemistry , phenylalanine hydroxylase , cofactor , molecule , phenylalanine , hydroxylation , dissociation (chemistry) , catalysis , active site , coordination sphere , crystal structure , ligand (biochemistry) , stereochemistry , crystallography , enzyme , amino acid , organic chemistry , biochemistry , receptor
Phenylalanine hydroxylase (PAH) catalyzes the hydroxylation of L ‐phenylalanine to L ‐tyrosine and is dependent on the contribution of electrons from the reduced cofactor tetrahydrobiopterin (BH 4 ). Whereas three ligating water molecules are bound to the central iron atom in the existing crystal structures of binary complexes of the catalytic domain of both the inactive, PAH–Fe III –BH 2 , and active, PAH–Fe II –BH 4 , forms of the human enzyme, previous spectroscopic studies show that the water molecules dissociate prior to the onset of the catalytic reaction. In the present study, starting from a cluster model of the active Fe II center of PAH, three successive water ligand dissociations followed by dioxygen coordination have been investigated by using density functional theory. The calculations show that the formation of the active, water‐free O 2 complex from the water‐ligated complex of the PAH–Fe II –BH 4 crystal structure is remarkably facile (Δ G = 1.5 kcal/mol). Moreover, the initial water dissociation is accompanied by entrance of the cofactor into the first coordination sphere of iron.