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Figure 1.
FIG. 1. Alternative pathways for the reaction of the
protein complex with oxygen in presence and absence of
substrate. In the first step of the catalytic mechanism of all
non-heme iron(II)-  KG dependent
dioxygenases, iron and the cosubstrate KG coordinate to the
protein. In the next step, the substrate molecule approaches the
active site (on the left), thereby displacing a water molecule
from the metal center and liberating a coordinatively
unsaturated iron atom. This facilitates dioxygen binding in the
next step. One oxygen atom of O[2] is transferred to the
cosubstrate, yielding succinate and carbon dioxide as reaction
products. The iron is thereby oxidized, and a ferryl Fe(IV)=O
species is formed, which then hydroxylates the substrate via a
radical intermediate. In the absence of substrate, coordination
of a dioxygen molecule to the iron(II)· KG
complex can take place (on the right). In a self-protecting
mechanism, one possible reaction pathway of the ferryl species
formed after the decarboxylation of the KG is the reaction with
an amino acid side chain such as tryptophan or tyrosine, as
shown for the KG-dependent
dioxygenases TfdA, AlkB, or TauD. As an alternative to this
self-hydroxylation mechanism, the ferryl intermediate could
react with a second cosubstrate molecule.
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