Post-translational modification of indoleamine 2,3-dioxygenase: N-terminal modification and nitration

Hidetsugu Fujigaki, Kanako Takahashi, Suwako Fujigaki, Junichi Masuda, Osamu Takikawa, Sanford P. Markey, Mitsuru Seishima, Kuniaki Saito

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Indoleamine 2,3-dioxygenase (IDO) induction can deplete l-Trp in target cells, and this effect is partially responsible for the antimicrobial, antiviral, and antiproliferative activities of several cytokines. Although a lot of studies have indicated the biological importance of IDO, the post-translational modification of IDO remains unknown. In this study, we analyzed IDO protein by liquid chromatography and tandem mass spectrometry (LC-MS/MS) to find post-translational modifications. LC-MS/MS analysis revealed that: (1) immunoprecipitated-IDO from a human monocyte cell line has been processed to cleave the N-terminal methionine, and the resulting N-terminal alanine is acetylated; (2) peroxynitrite, an NO-derived reactive species, which can modify proteins via formation of 3-nitrotyrosine, induced nitration and inactivation of recombinant IDO, specifically nitrating Tyr15, 345, and 353 residues. We successfully revealed these two types of post-translational modifications of IDO, and further findings of the post-translational modification may shed light on the mechanisms of IDO induction.

Original languageEnglish
Pages (from-to)41-45
Number of pages5
JournalInternational Congress Series
Volume1304
DOIs
Publication statusPublished - 01-11-2007

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Post Translational Protein Processing
Peroxynitrous Acid
Tandem Mass Spectrometry
Liquid Chromatography
Alanine
Methionine
Antiviral Agents
Monocytes
Proteins
Cytokines
Cell Line

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Fujigaki, Hidetsugu ; Takahashi, Kanako ; Fujigaki, Suwako ; Masuda, Junichi ; Takikawa, Osamu ; Markey, Sanford P. ; Seishima, Mitsuru ; Saito, Kuniaki. / Post-translational modification of indoleamine 2,3-dioxygenase : N-terminal modification and nitration. In: International Congress Series. 2007 ; Vol. 1304. pp. 41-45.
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abstract = "Indoleamine 2,3-dioxygenase (IDO) induction can deplete l-Trp in target cells, and this effect is partially responsible for the antimicrobial, antiviral, and antiproliferative activities of several cytokines. Although a lot of studies have indicated the biological importance of IDO, the post-translational modification of IDO remains unknown. In this study, we analyzed IDO protein by liquid chromatography and tandem mass spectrometry (LC-MS/MS) to find post-translational modifications. LC-MS/MS analysis revealed that: (1) immunoprecipitated-IDO from a human monocyte cell line has been processed to cleave the N-terminal methionine, and the resulting N-terminal alanine is acetylated; (2) peroxynitrite, an NO-derived reactive species, which can modify proteins via formation of 3-nitrotyrosine, induced nitration and inactivation of recombinant IDO, specifically nitrating Tyr15, 345, and 353 residues. We successfully revealed these two types of post-translational modifications of IDO, and further findings of the post-translational modification may shed light on the mechanisms of IDO induction.",
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Post-translational modification of indoleamine 2,3-dioxygenase : N-terminal modification and nitration. / Fujigaki, Hidetsugu; Takahashi, Kanako; Fujigaki, Suwako; Masuda, Junichi; Takikawa, Osamu; Markey, Sanford P.; Seishima, Mitsuru; Saito, Kuniaki.

In: International Congress Series, Vol. 1304, 01.11.2007, p. 41-45.

Research output: Contribution to journalArticle

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T1 - Post-translational modification of indoleamine 2,3-dioxygenase

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AU - Fujigaki, Hidetsugu

AU - Takahashi, Kanako

AU - Fujigaki, Suwako

AU - Masuda, Junichi

AU - Takikawa, Osamu

AU - Markey, Sanford P.

AU - Seishima, Mitsuru

AU - Saito, Kuniaki

PY - 2007/11/1

Y1 - 2007/11/1

N2 - Indoleamine 2,3-dioxygenase (IDO) induction can deplete l-Trp in target cells, and this effect is partially responsible for the antimicrobial, antiviral, and antiproliferative activities of several cytokines. Although a lot of studies have indicated the biological importance of IDO, the post-translational modification of IDO remains unknown. In this study, we analyzed IDO protein by liquid chromatography and tandem mass spectrometry (LC-MS/MS) to find post-translational modifications. LC-MS/MS analysis revealed that: (1) immunoprecipitated-IDO from a human monocyte cell line has been processed to cleave the N-terminal methionine, and the resulting N-terminal alanine is acetylated; (2) peroxynitrite, an NO-derived reactive species, which can modify proteins via formation of 3-nitrotyrosine, induced nitration and inactivation of recombinant IDO, specifically nitrating Tyr15, 345, and 353 residues. We successfully revealed these two types of post-translational modifications of IDO, and further findings of the post-translational modification may shed light on the mechanisms of IDO induction.

AB - Indoleamine 2,3-dioxygenase (IDO) induction can deplete l-Trp in target cells, and this effect is partially responsible for the antimicrobial, antiviral, and antiproliferative activities of several cytokines. Although a lot of studies have indicated the biological importance of IDO, the post-translational modification of IDO remains unknown. In this study, we analyzed IDO protein by liquid chromatography and tandem mass spectrometry (LC-MS/MS) to find post-translational modifications. LC-MS/MS analysis revealed that: (1) immunoprecipitated-IDO from a human monocyte cell line has been processed to cleave the N-terminal methionine, and the resulting N-terminal alanine is acetylated; (2) peroxynitrite, an NO-derived reactive species, which can modify proteins via formation of 3-nitrotyrosine, induced nitration and inactivation of recombinant IDO, specifically nitrating Tyr15, 345, and 353 residues. We successfully revealed these two types of post-translational modifications of IDO, and further findings of the post-translational modification may shed light on the mechanisms of IDO induction.

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