Indoleamine 2,3-dioxygenase 1

Function

Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway. Involved in the peripheral immune tolerance, contributing to maintain homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses. Tryptophan shortage inhibits T lymphocytes division and accumulation of tryptophan catabolites induces T-cell apoptosis and differentiation of regulatory T-cells. Acts as a suppressor of anti-tumor immunity. Limits the growth of intracellular pathogens by depriving tryptophan. Protects the fetus from maternal immune rejection.

Classification

Family (Pfam)

PF01231 IDO

InterPro

Indolamine_dOase, Trp/Indoleamine_2_3_dOase-like

Functional cluster

Zinc-Finger & Ubiquitination Proteins

Experimental structures · PDB · 85

• 2D0T X-ray 2.30A
• 2D0U X-ray 3.40A
• 4PK5 X-ray 2.79A
• 4PK6 X-ray 3.45A
• 4U72 X-ray 2.00A
• 4U74 X-ray 2.31A
• 5EK2 X-ray 2.68A
• 5EK3 X-ray 2.21A
• 5EK4 X-ray 2.64A
• 5ETW X-ray 2.70A
• 5WHR X-ray 2.28A
• 5WMU X-ray 2.40A
• … and 73 more

A predicted model is available from AlphaFold.

Gene Ontology · 16

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0030485 smooth muscle contractile fiber
• GO:0032421 stereocilium bundle
• GO:0009055 electron transfer activity
• GO:0020037 heme binding
• GO:0033754 indoleamine 2,3-dioxygenase activity
• GO:0004833 L-tryptophan 2,3-dioxygenase activity
• GO:0046872 metal ion binding
• GO:0034354 'de novo' NAD+ biosynthetic process from L-tryptophan
• GO:0007565 female pregnancy
• GO:0002376 immune system process
• GO:0006569 L-tryptophan catabolic process
• GO:0019441 L-tryptophan catabolic process to L-kynurenine
• GO:0070234 positive regulation of T cell apoptotic process
• GO:0019805 quinolinate biosynthetic process

Drugs targeting this protein · 2

• EPACADOSTAT inhibitor
• LINRODOSTAT inhibitor

Related proteins · sequence + function similarity

• Indoleamine 2,3-dioxygenase 1 0.94
• Indoleamine 2,3-dioxygenase 1 0.93
• Indoleamine 2,3-dioxygenase 2 0.85
• Indoleamine 2,3-dioxygenase 2 0.85
• Indoleamine 2,3-dioxygenase 2 0.85
• Indoleamine 2,3-dioxygenase qulI 0.84
• Indoleamine 2,3-dioxygenase tpzB 0.82
• Indoleamine 2,3-dioxygenase acdA 0.82
• Indoleamine 2,3-dioxygenase nanC 0.81
• Myoglobin 0.81
• Indoleamine 2,3-dioxygenase 0.81
• 6-hydroxytryptophan 2,3-dioxygenase fscD 0.81

Co-cited proteins · studied together in the literature

• Indoleamine 2,3-dioxygenase 2 5 shared papers
• Indoleamine 2,3-dioxygenase 2 3 shared papers
• Indoleamine 2,3-dioxygenase 1 2 shared papers

Literature · 21 cited papers

• Expression profile of the human IDO1 protein, a cancer drug target involved in tumoral immune resistance. OncoImmunology · 2015
• Challenges in the discovery of indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors. J. Med. Chem. · 2015
• Low efficiency IDO2 enzymes are conserved in lower vertebrates, whereas higher efficiency IDO1 enzymes are dispensable. FEBS J. · 2015
• Tryptophan-degrading enzymes in tumoral immune resistance. Front. Immunol. · 2015
• Heme-binding-mediated negative regulation of the tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) by IDO2. Exp. Mol. Med. · 2014
• Crystal structures and structure-activity relationships of imidazothiazole derivatives as IDO1 inhibitors. ACS Med. Chem. Lett. · 2014
• New insights into IDO biology in bacterial and viral infections. Front. Immunol. · 2014
• Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends Immunol. · 2013
• IDO1 and IDO2 are expressed in human tumors: levo- but not dextro-1-methyl tryptophan inhibits tryptophan catabolism. Cancer Immunol. Immunother. · 2009
• Evolution of vertebrate indoleamine 2,3-dioxygenases. J. Mol. Evol. · 2007
• Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan. Cancer Res. · 2007
• Cytochrome b(5) is a major reductant in vivo of human indoleamine 2,3-dioxygenase expressed in yeast. FEBS Lett. · 2006
• … and 9 more in the literature graph