Inhibition of indoleamine 2,3 dioxygenase activity by H2O2
Journal article
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, Peminder and Smythe, George A.. (2006). Inhibition of indoleamine 2,3 dioxygenase activity by H2O2. Archives of Biochemistry and Biophysics. 450(1), pp. 9 - 19. https://doi.org/10.1016/j.abb.2006.03.003
Authors | 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, Peminder and Smythe, George A. |
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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. |
Keywords | indoleamine 2; 3-dioxygenase; hydrogen peroxide; inhibition; kynurenine pathway; tryptophan metabolism; cysteine; oxidation |
Year | 2006 |
Journal | Archives of Biochemistry and Biophysics |
Journal citation | 450 (1), pp. 9 - 19 |
Publisher | Academic Press |
ISSN | 0003-9861 |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.abb.2006.03.003 |
Scopus EID | 2-s2.0-33646858094 |
Page range | 9 - 19 |
Research Group | School of Behavioural and Health Sciences |
Publisher's version | File Access Level Controlled |
Place of publication | United States of America |
https://acuresearchbank.acu.edu.au/item/85x70/inhibition-of-indoleamine-2-3-dioxygenase-activity-by-h2o2
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