Substrate Oxidation by Indoleamine 2,3-Dioxygenase

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 to N-formylkynurenine. This is an O2-dependent process and catalyzed by indol...

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Bibliographic Details
Published inThe Journal of biological chemistry Vol. 290; no. 52; pp. 30924 - 30930
Main Authors Booth, Elizabeth S., Basran, Jaswir, Lee, Michael, Handa, Sandeep, Raven, Emma L.
Format Journal Article
LanguageEnglish
Published Elsevier Inc 01.12.2015
Subjects
dioxygenase
enzyme mechanism
heme
indoleamine 2,3-dioxygenase
substrate specificity
tryptophan
dioxygenase
indoleamine 2,3-dioxygenase
enzyme mechanism
heme
tryptophan
substrate specificity
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Summary: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 to N-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, 237–244), 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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M115.695684