Inhibition of Indoleamine 2,3 Dioxygenase Activity by H2O2

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avondale-bepress-to-dspace.facultyNursing
avondale-bepress-to-dspace.peer_review_statusPeer reviewed before publication
avondale-bepress.abstract<p>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 H<sub>2</sub>O<sub>2</sub> is at least partially reversible in vitro. We present evidence that cysteine oxidation represents one mechanism of indoleamine 2,3-dioxygenase inhibition.</p>
avondale-bepress.articleid1017
avondale-bepress.authorsAnne Poljak
avondale-bepress.authorsRoss Grant
avondale-bepress.authorsChris J Austin
avondale-bepress.authorsJoanne F Jamie
avondale-bepress.authorsRobert D Willows
avondale-bepress.authorsOsamu Takikawa
avondale-bepress.authorsTamantha K Littlejohn
avondale-bepress.authorsRoger J Truscott
avondale-bepress.authorsMark J Walker
avondale-bepress.authorsPerminder Sachdev
avondale-bepress.authorsGeorge A Smythe
avondale-bepress.context-key3184986
avondale-bepress.coverpage-urlhttps://research.avondale.edu.au/nh_papers/18
avondale-bepress.document-typearticle
avondale-bepress.field.author_faculty_disciplineNursing
avondale-bepress.field.comments<p>Due to copyright restrictions this article is unavailable for download.</p> <p>Staff and Students of Avondale College may access the full text of this article via library PRIMO search <a href="http://www.avondale.edu.au/library">here.</a></p> <p><em>Archives of Biochemistry and Biophysics</em> may be accessed <a href="http://www.journals.elsevier.com/archives-of-biochemistry-and-biophysics/#description">here</a></p>
avondale-bepress.field.create_openurltrue
avondale-bepress.field.custom_citation<p>Poljak, A., Grant, R., Austin, C., Jamie, J., Willows, R., Takikawa, O., . . . Smythe, G. (2006). Inhibition of indoleamine 2,3 dioxygenase activity by H<sub>2</sub>O<sub>2</sub>. <em>Archives of Biochemistry and Biophysics, 450</em>(1), 9-19. doi:10.1016/j.abb.2006.03.003</p>
avondale-bepress.field.doihttps://doi.org/10.1016/j.abb.2006.03.003
avondale-bepress.field.embargo_date2012-08-06T00:00:00Z
avondale-bepress.field.issn0003-9861
avondale-bepress.field.issue_number1
avondale-bepress.field.journalArchives of Biochemistry and Biophysics
avondale-bepress.field.page_numbers9-19
avondale-bepress.field.peer_reviewBefore publication
avondale-bepress.field.publication_date2006-06-01T00:00:00Z
avondale-bepress.field.source_fulltext_urlhttp://www.sciencedirect.com/science/article/pii/S0003986106000920
avondale-bepress.field.source_publication<p>This article was originally published as:</p> <p>Poljak, A., Grant, R., Austin, C., Jamie, J., Willows, R., Takikawa, O., . . . Smythe, G. (2006). Inhibition of indoleamine 2,3 dioxygenase activity by H<sub>2</sub>O<sub>2</sub>. <em>Archives of Biochemistry and Biophysics, 450</em>(1), 9-19. doi:10.1016/j.abb.2006.03.003</p><p>ISSN:0003-9861</p>
avondale-bepress.field.volume_number450
avondale-bepress.keywordsIndoleamine 2 3-dioxygenase
avondale-bepress.keywordsHydrogen peroxide
avondale-bepress.keywordsInhibition; Kynurenine pathway
avondale-bepress.keywordsTryptophan metabolism
avondale-bepress.keywordsCysteine
avondale-bepress.keywordsOxidation
avondale-bepress.label18
avondale-bepress.publication-date2006-06-01T00:00:00Z
avondale-bepress.publication-titleNursing and Health Papers and Journal Articles
avondale-bepress.statepublished
avondale-bepress.submission-date2012-08-06T23:06:41Z
avondale-bepress.submission-pathnh_papers/18
avondale-bepress.titleInhibition of Indoleamine 2,3 Dioxygenase Activity by H2O2
avondale-bepress.typearticle
dc.contributor.authorSmythe, George A.
dc.contributor.authorSachdev, Perminder
dc.contributor.authorWalker, Mark J.
dc.contributor.authorTruscott, Roger J.
dc.contributor.authorLittlejohn, Tamantha K.
dc.contributor.authorTakikawa, Osamu
dc.contributor.authorWillows, Robert D.
dc.contributor.authorJamie, Joanne F.
dc.contributor.authorAustin, Chris J.
dc.contributor.authorGrant, Ross
dc.contributor.authorPoljak, Anne
dc.date.accessioned2023-11-01T00:27:19Z
dc.date.available2023-11-01T00:27:19Z
dc.date.issued2006-06-01
dc.date.submitted2012-08-06T23:06:41Z
dc.description.abstract<p>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 H<sub>2</sub>O<sub>2</sub> is at least partially reversible in vitro. We present evidence that cysteine oxidation represents one mechanism of indoleamine 2,3-dioxygenase inhibition.</p>
dc.description.versionBefore publication
dc.identifier.citation<p>Poljak, A., Grant, R., Austin, C., Jamie, J., Willows, R., Takikawa, O., . . . Smythe, G. (2006). Inhibition of indoleamine 2,3 dioxygenase activity by H<sub>2</sub>O<sub>2</sub>. <em>Archives of Biochemistry and Biophysics, 450</em>(1), 9-19. doi:10.1016/j.abb.2006.03.003</p>
dc.identifier.doihttps://doi.org/10.1016/j.abb.2006.03.003
dc.identifier.issn0003-9861
dc.identifier.urihttps://research.avondale.edu.au/handle/123456789/03184986
dc.language.isoen_us
dc.provenance<p>This article was originally published as:</p> <p>Poljak, A., Grant, R., Austin, C., Jamie, J., Willows, R., Takikawa, O., . . . Smythe, G. (2006). Inhibition of indoleamine 2,3 dioxygenase activity by H<sub>2</sub>O<sub>2</sub>. <em>Archives of Biochemistry and Biophysics, 450</em>(1), 9-19. doi:10.1016/j.abb.2006.03.003</p><p>ISSN:0003-9861</p>
dc.rights<p>Due to copyright restrictions this article is unavailable for download.</p> <p>Staff and Students of Avondale College may access the full text of this article via library PRIMO search <a href="http://www.avondale.edu.au/library">here.</a></p> <p><em>Archives of Biochemistry and Biophysics</em> may be accessed <a href="http://www.journals.elsevier.com/archives-of-biochemistry-and-biophysics/#description">here</a></p>
dc.subjectIndoleamine 2 3-dioxygenase
dc.subjectHydrogen peroxide
dc.subjectInhibition; Kynurenine pathway
dc.subjectTryptophan metabolism
dc.subjectCysteine
dc.subjectOxidation
dc.titleInhibition of Indoleamine 2,3 Dioxygenase Activity by H2O2
dc.typeJournal Article
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