The initial formation of the ternary complex (1) occurs by substrate binding, followed by dioxygen binding to the ferrous protein. The ternary complex activates O2 and allows the otherwise spin-forbidden reaction to proceeed. The formation of the hydroperoxide intermediate (2) is catalyzed by the loss of the indole proton. Two mechanisms are possible: base-catalysed deprotonation or proton abstraction by bound dioxygen. However, catalysis by the ironbound dioxygen is generally proposed, as a result of experiments showing that catalytic activity is maintained upon substitution of alanine for His55 (the only basic residue in the active site of the enzyme).
The rearrangement of the hydroperoxide intermediate to form the product could occur via the dioxetane intermediate (see figure) or a Criegee intermediate. However, density functional theory calculations on the catalytic mechanism of tryptophan 2,3-dioxygenase have cast doubt on the relevance of the Criegee mechanism.
Read more about this topic: Tryptophan 2,3-dioxygenase
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