Substrate oxidation by indoleamine 2,3-dioxygenase: Evidence for a common reaction mechanism

Elizabeth S. Booth, Jaswir Basran, Michael Lee, Sandeep Handa, Emma L. Raven*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

22 Citations (Scopus)

Abstract

The kynurenine pathway is the major route of L-tryptophan (L-Trp) catabolism in biology, leading ultimately to the formation of NAD+. The initial and rate-limiting step of the kynurenine pathway involves oxidation of L-Trp toN-formylkynurenine. This is an O2-dependent process and catalyzed by indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase. More than 60 years after these dioxygenase enzymes were first isolated (Kotake, Y., and Masayama, I. (1936)Z. Physiol. Chem. 243, 237â€" 244), the mechanism of the reaction is not established. We examined the mechanism of substrate oxidation for a series of substituted tryptophan analogues by indoleamine 2,3-dioxygenase. We observed formation of a transient intermediate, assigned as a Compound II (ferryl) species, during oxidation of L-Trp, 1-methyl-L-Trp, and a number of other substrate analogues. The data are consistent with a common reaction mechanism for indoleamine 2,3-dioxygenase-catalyzed oxidation of tryptophan and other tryptophan analogues.

Original languageEnglish
Pages (from-to)30924-30930
Number of pages7
JournalJournal of Biological Chemistry
Volume290
Issue number52
DOIs
Publication statusPublished - 25 Dec 2015

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