Inhibition of indoleamine 2,3 dioxygenase activity by H2O2

Poljak, Anne, Grant, Ross, Austin, Chris J. D., Jamie, Joanne F., Willows, Robert D., Takikawa, Osamu, Littlejohn, Tamantha K., Truscott, Roger J. W., Walker, Mark J., Sachdev, Perminder and Smythe, George A. (2006) Inhibition of indoleamine 2,3 dioxygenase activity by H2O2. Archives of Biochemistry and Biophysics, 450 1: 9-19. doi:10.1016/

Author Poljak, Anne
Grant, Ross
Austin, Chris J. D.
Jamie, Joanne F.
Willows, Robert D.
Takikawa, Osamu
Littlejohn, Tamantha K.
Truscott, Roger J. W.
Walker, Mark J.
Sachdev, Perminder
Smythe, George A.
Title Inhibition of indoleamine 2,3 dioxygenase activity by H2O2
Formatted title
Inhibition of indoleamine 2,3 dioxygenase activity by H2O2
Journal name Archives of Biochemistry and Biophysics   Check publisher's open access policy
ISSN 0003-9861
Publication date 2006-06
Sub-type Article (original research)
DOI 10.1016/
Volume 450
Issue 1
Start page 9
End page 19
Total pages 11
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Language eng
Formatted abstract
Indoleamine 2,3-dioxygenase is the first and rate limiting enzyme of the kynurenine pathway of tryptophan metabolism, has potent effects on cell proliferation and mediates antimicrobial, antitumorogenic, and immunosuppressive effects. As a potent cytotoxic effector, the mechanisms of indoleamine 2,3-dioxygenase inhibition deserve greater attention. The work presented here represents the first systematic study exploring the mechanisms by which low levels of hydrogen peroxide (10–100 μM) inhibit indoleamine 2,3-dioxygenase in vitro. Following brief peroxide exposure both enzyme inhibition and structural changes were observed. Loss of catalysis was accompanied by oxidation of several cysteine residues to sulfinic and sulfonic acids, observed by electrospray and MALDI mass spectrometry. Enzyme activity could in part be preserved in the presence of sulfhydryl containing compounds, particularly DTT and methionine. However, these structural alterations did not prevent substrate (l-tryptophan) binding. Some enzyme activity could be recovered in the presence of thioredoxin, indicating that the inhibitory effect of H2O2 is at least partially reversible in vitro. We present evidence that cysteine oxidation represents one mechanism of indoleamine 2,3-dioxygenase inhibition.
Keyword Indoleamine 2,3-dioxygenase
Hydrogen peroxide
Kynurenine pathway
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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