Please use this identifier to cite or link to this item:
Title: Analysis of Reaction Intermediates in Tryptophan 2,3-Dioxygenase: A Comparison with Indoleamine 2,3-Dioxygenase.
Authors: Basran, Jaswir
Booth, Elizabeth S.
Lee, Michael
Handa, Sandeep
Raven, Emma L.
First Published: 1-Dec-2016
Publisher: American Chemical Society
Citation: Biochemistry, 2016, 55 (49), pp. 6743-6750
Abstract: Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are heme-containing enzymes that catalyze the O2-dependent oxidation of l-tryptophan (l-Trp) in biological systems. Although many decades have passed since their discovery, the mechanism of tryptophan oxidation has not been established. It has been widely assumed that IDO and TDO react using the same mechanism, although there is no evidence that they do. For IDO, a Compound II (ferryl) species accumulates in the steady state and is implicated in the mechanism; in TDO, no such species has ever been observed. In this paper, we examine the kinetics of tryptophan oxidation in TDO. We find no evidence for the accumulation of Compound II during TDO catalysis. Instead, a ternary [Fe(II)-O2, l-Trp] complex is detected under steady state conditions. The absence of a Compound II species in the steady state in TDO is not due to an intrinsic inability of the TDO enzyme to form ferryl heme, because Compound II can be formed directly through a different route in which ferrous heme is reacted with peroxide. We interpret the data to mean that the rate-limiting step in the IDO and TDO mechanisms is not the same.
DOI Link: 10.1021/acs.biochem.6b01005
ISSN: 0006-2960
eISSN: 1520-4995
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2016, American Chemical Society. Deposited with reference to the publisher’s open access archiving policy.
Description: The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.biochem.6b01005. Reactivity of XcTDO with O2 (Figure S1), formation of the [Fe(II)−O2, L-Trp] ternary complex in TDOs (Figure S2), oxidation of 5-fluoro-Trp by ferrous XcTDO (Figure S3), and formation of Compound II in TDO in the presence of substrate (Figure S4) (PDF)
Appears in Collections:Published Articles, Dept. of Chemistry

Files in This Item:
File Description SizeFormat 
s1-ln2260241-929977255-1939656818Hwf552846218IdV10905218562260241PDF_HI0001.pdfPost-review (final submitted author manuscript)421.15 kBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.