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Title: The mechanism of formation of N-formylkynurenine by heme dioxygenases.
Authors: Basran, J
Efimov, I
Chauhan, N
Thackray, SJ
Krupa, JL
Eaton, G
Griffith, GA
Mowat, CG
Handa, S
Raven, EL
First Published: 12-Oct-2011
Citation: J AM CHEM SOC, 2011, 133 (40), pp. 16251-16257
Abstract: Heme dioxygenases catalyze the oxidation of L-tryptophan to N-formylkynurenine (NFK), the first and rate-limiting step in tryptophan catabolism. Although recent progress has been made on early stages in the mechanism, there is currently no experimental data on the mechanism of product (NFK) formation. In this work, we have used mass spectrometry to examine product formation in a number of dioxygenases. In addition to NFK formation (m/z = 237), the data identify a species (m/z = 221) that is consistent with insertion of a single atom of oxygen into the substrate during O(2)-driven turnover. The fragmentation pattern for this m/z = 221 species is consistent with a cyclic amino acetal structure; independent chemical synthesis of the 3a-hydroxypyrroloindole-2-carboxylic acid compound is in agreement with this assignment. Labeling experiments with (18)O(2) confirm the origin of the oxygen atom as arising from O(2)-dependent turnover. These data suggest that the dioxygenases use a ring-opening mechanism during NFK formation, rather than Criegee or dioxetane mechanisms as previously proposed.
DOI Link: 10.1021/ja207066z
eISSN: 1520-5126
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Chemistry

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