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Title: Reassessment of the reaction mechanism in the heme dioxygenases.
Authors: Chauhan, N
Thackray, SJ
Rafice, SA
Eaton, G
Lee, M
Efimov, I
Basran, J
Jenkins, PR
Mowat, CG
Chapman, SK
Raven, EL
First Published: 1-Apr-2009
Citation: J AM CHEM SOC, 2009, 131 (12), pp. 4186-4187
Abstract: Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are heme enzymes that catalyze the O(2)-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 N(1) is not essential for catalysis, and an alternative reaction mechanism, based on the known chemistry of indoles, is presented.
DOI Link: 10.1021/ja808326g
eISSN: 1520-5126
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Chemistry

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