Reassessment of the reaction mechanism in the heme dioxygenases

Nishma Chauhan*, Sarah J. Thackray, Sara A. Rafice, Graham Eaton, Michael Lee, Igor Efimov, Jaswir Basran, Paul R. Jenkins, Christopher G. Mowat, Stephen K. Chapman, Emma Lloyd Raven

*Corresponding author for this work

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

58 Citations (Scopus)

Abstract

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are heme enzymes that catalyze the O2-dependent oxidation of L-tryptophan to N-formyl-kynurenine. Previous proposals for the mechanism of this reaction have suggested that deprotonation of the indole NH group, either by an active-site base or by oxygen bound to the heme iron, as the initial step. In this work, we have examined the activity of 1-Me-L-Trp with three different heme dioxygenases and their site-directed variants. We find, in contrast to previous work, that 1-Me-L-Trp is a substrate for the heme dioxygenase enzymes. These observations suggest that deprotonation of the indole N1 is not essential for catalysis, and an alternative reaction mechanism, based on the known chemistry of indoles, is presented.

Original languageEnglish
Pages (from-to)4186-4187
Number of pages2
JournalJournal of the American Chemical Society
Volume131
Issue number12
DOIs
Publication statusPublished - 1 Apr 2009

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