title: Posttranslational modification of indoleamine 2,3-dioxygenase.
abstract: Protein posttranslational modifications (PTMs) perform essential roles in the biological regulation of a cell. PTMs are extremely important because they can change a protein's physical or chemical properties, conformation, activity, cellular location, or stability. In fact, most proteins are altered by the addition or removal of a chemical moiety on either an amino acid or the protein's N- or C-terminus. Some PTMs can be added and removed dynamically as a mechanism for reversibly controlling protein function. Thus, identifying the PTM sites is critical to fully understand the biological roles of any given protein. Mass spectrometry (MS) is a widely used analytical strategy to identify PTMs. We have used an automated two-dimensional liquid chromatography (LC) system coupled with electrospray ionization quadrupole ion-trap MS to identify PTMs for indoleamine 2,3-dioxygenase 1 (IDO1), one of the tryptophan catabolic enzymes. IDO1 promotes immune tolerance by suppressing local T-cell responses under various physiological and pathophysiological conditions, such as pregnancy in mammals, tumor resistance, autoimmunity, and chronic inflammation. Although many studies have demonstrated the biological importance of IDO activity, the PTMs of IDO enzymes remain largely unknown. Only a few important PTMs of IDO1 have been found, such as nitration, N-terminal acetylation, and phosphorylation. In this review, we analyze the PTMs of IDO1 using our two-dimensional LC-MS/MS system, and provide an overview of our current understanding.
authors.affiliation: Faculty of Health Sciences, Hiroshima International University, 555-36 Kurose-Gakuendai, Higashi-Hiroshima City, Hiroshima 739-2695, Japan. h-fuji@hs.hirokoku-u.ac.jp
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Fujigaki
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Seishima
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Saito
mesh_terms: D000595:Amino Acid Sequence; D002853:Chromatography, Liquid; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D017386:Sequence Homology, Amino Acid; D053719:Tandem Mass Spectrometry
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase