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drug target
as an immunosuppressive enzyme, indoleamine 2,3-dioxygenase 1 is considered a promising target for oncology immunotherapy
drug target
combined treatment of cancer cells in vitro with indoleamine 2,3-dioxygenase 1-specific antisense oligonucleotides and small molecule inhibitors can reduce the production of kynurenine by cancer cells in a synergistic manner
drug target
conversion of tryptophan to N-formylkynurenine is the first and rate-limiting step of the tryptophan metabolic pathway (i.e., the kynurenine pathway). This conversion is catalyzed by three enzyme isoforms: indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan-2,3-dioxygenase (TDO). As this pathway generates numerous metabolites that are involved in various pathological conditions, IDOs and TDO represent important targets for therapeutic intervention. Despite their poor sequence similarities, their active sites are highly conserved, and therefore allow the design of inhibitors with multiple activities that can target at least two isoforms
drug target
human indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan 2,3-dioxygenase (hTDO) are closely linked to the pathogenesis of Parkinson's disease
drug target
Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are promising drug development targets due to their implications in pathologies such as cancer and neurodegenerative diseases. IDO1/TDO dual inhibitors and provides chemical molecules for potential development into drugs
drug target
the enzyme is a promising target for cancer immunotherapy
drug target
the enzyme is a tumour cell survival factor that causes immune escape in several types of cancer
drug target
the enzyme is an anti-cancer drug target
drug target
the enzyme is an attractive target for cancer immunotherapy
evolution
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indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview. Some lineages have independently generated multiple IDO paralogues through gene duplications. Only mammalian IDO1s and fungal typical IDOs have high affinity and catalytic efficiency for L-Trp catabolism, comparable to TDOs. Invertebrate IDO enzymes have low affinity and catalytic efficiency for L-Trp catabolism. Phylogenetic analysis. the phylogenetic distribution of low catalytic-efficiency IDOs indicates the ancestral IDO also had low affinity and catalytic efficiency for L-Trp catabolism. IDOs with high catalytic-efficiency for L-Trp catabolism may have evolved in certain lineages to fulfill particular biological roles. The low catalytic efficiency IDOs have been well conserved in a number of lineages throughout their evolution, although it is not clear that the enzymes contribute significantly to L-Trp catabolism in these species
evolution
indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview. Some lineages have independently generated multiple IDO paralogues through gene duplications. Only mammalian IDO1s and fungal typical IDOs have high affinity and catalytic efficiency for L-Trp catabolism, comparable to TDOs. Invertebrate IDO enzymes have low affinity and catalytic efficiency for L-Trp catabolism. Phylogenetic analysis. the phylogenetic distribution of low catalytic-efficiency IDOs indicates the ancestral IDO also had low affinity and catalytic efficiency for L-Trp catabolism. IDOs with high catalytic-efficiency for L-Trp catabolism may have evolved in certain lineages to fulfill particular biological roles. The low catalytic efficiency IDOs have been well conserved in a number of lineages throughout their evolution, although it is not clear that the enzymes contribute significantly to L-Trp catabolism in these species
evolution
indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview. Some lineages have independently generated multiple IDO paralogues through gene duplications. Only mammalian IDO1s and fungal typical IDOs have high affinity and catalytic efficiency for L-Trp catabolism, comparable to TDOs. Invertebrate IDO enzymes have low affinity and catalytic efficiency for L-Trp catabolism. Phylogenetic analysis. the phylogenetic distribution of low catalytic-efficiency IDOs indicates the ancestral IDO also had low affinity and catalytic efficiency for L-Trp catabolism. IDOs with high catalytic-efficiency for L-Trp catabolism may have evolved in certain lineages to fulfill particular biological roles. The low catalytic efficiency IDOs have been well conserved in a number of lineages throughout their evolution, although it is not clear that the enzymes contribute significantly to L-Trp catabolism in these species
evolution
indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview. Some lineages have independently generated multiple IDO paralogues through gene duplications. Only mammalian IDO1s and fungal typical IDOs have high affinity and catalytic efficiency for L-Trp catabolism, comparable to TDOs. Invertebrate IDO enzymes have low affinity and catalytic efficiency for L-Trp catabolism. Phylogenetic analysis. the phylogenetic distribution of low catalytic-efficiency IDOs indicates the ancestral IDO also had low affinity and catalytic efficiency for L-Trp catabolism. IDOs with high catalytic-efficiency for L-Trp catabolism may have evolved in certain lineages to fulfill particular biological roles. The low catalytic efficiency IDOs have been well conserved in a number of lineages throughout their evolution, although it is not clear that the enzymes contribute significantly to L-Trp catabolism in these species
evolution
indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview. Some lineages have independently generated multiple IDO paralogues through gene duplications. Only mammalian IDO1s and fungal typical IDOs have high affinity and catalytic efficiency for L-Trp catabolism, comparable to TDOs. Invertebrate IDO enzymes have low affinity and catalytic efficiency for L-Trp catabolism. Phylogenetic analysis. the phylogenetic distribution of low catalytic-efficiency IDOs indicates the ancestral IDO also had low affinity and catalytic efficiency for L-Trp catabolism. IDOs with high catalytic-efficiency for L-Trp catabolism may have evolved in certain lineages to fulfill particular biological roles. The low catalytic efficiency IDOs have been well conserved in a number of lineages throughout their evolution, although it is not clear that the enzymes contribute significantly to L-Trp catabolism in these species
evolution
indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview. Some lineages have independently generated multiple IDO paralogues through gene duplications. Only mammalian IDO1s and fungal typical IDOs have high affinity and catalytic efficiency for L-Trp catabolism, comparable to TDOs. Invertebrate IDO enzymes have low affinity and catalytic efficiency for L-Trp catabolism. Phylogenetic analysis. the phylogenetic distribution of low catalytic-efficiency IDOs indicates the ancestral IDO also had low affinity and catalytic efficiency for L-Trp catabolism. IDOs with high catalytic-efficiency for L-Trp catabolism may have evolved in certain lineages to fulfill particular biological roles. The low catalytic efficiency IDOs have been well conserved in a number of lineages throughout their evolution, although it is not clear that the enzymes contribute significantly to L-Trp catabolism in these species
evolution
indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview. Some lineages have independently generated multiple IDO paralogues through gene duplications. Only mammalian IDO1s and fungal typical IDOs have high affinity and catalytic efficiency for L-Trp catabolism, comparable to TDOs. Invertebrate IDO enzymes have low affinity and catalytic efficiency for L-Trp catabolism. Phylogenetic analysis. the phylogenetic distribution of low catalytic-efficiency IDOs indicates the ancestral IDO also had low affinity and catalytic efficiency for L-Trp catabolism. IDOs with high catalytic-efficiency for L-Trp catabolism may have evolved in certain lineages to fulfill particular biological roles. The low catalytic efficiency IDOs have been well conserved in a number of lineages throughout their evolution, although it is not clear that the enzymes contribute significantly to L-Trp catabolism in these species
evolution
indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview. Some lineages have independently generated multiple IDO paralogues through gene duplications. Only mammalian IDO1s and fungal typical IDOs have high affinity and catalytic efficiency for L-Trp catabolism, comparable to TDOs. Invertebrate IDO enzymes have low affinity and catalytic efficiency for L-Trp catabolism. Phylogenetic analysis. the phylogenetic distribution of low catalytic-efficiency IDOs indicates the ancestral IDO also had low affinity and catalytic efficiency for L-Trp catabolism. IDOs with high catalytic-efficiency for L-Trp catabolism may have evolved in certain lineages to fulfill particular biological roles. The low catalytic efficiency IDOs have been well conserved in a number of lineages throughout their evolution, although it is not clear that the enzymes contribute significantly to L-Trp catabolism in these species
evolution
indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview. Some lineages have independently generated multiple IDO paralogues through gene duplications. Only mammalian IDO1s and fungal typical IDOs have high affinity and catalytic efficiency for L-Trp catabolism, comparable to TDOs. Invertebrate IDO enzymes have low affinity and catalytic efficiency for L-Trp catabolism. Phylogenetic analysis. the phylogenetic distribution of low catalytic-efficiency IDOs indicates the ancestral IDO also had low affinity and catalytic efficiency for L-Trp catabolism. IDOs with high catalytic-efficiency for L-Trp catabolism may have evolved in certain lineages to fulfill particular biological roles. The low catalytic efficiency IDOs have been well conserved in a number of lineages throughout their evolution, although it is not clear that the enzymes contribute significantly to L-Trp catabolism in these species
malfunction
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IDO deficiency leads to diminished phenotypic and functional maturation of dendritic cells in vitro and in vivo
malfunction
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IDO inhibition significantly affects the ability of CD103+ dendritic cells to promote conversion of naive T cells into Foxp3+Tregs while the ability of CD103- cells is unaffected. IDO inhibition impinges on the development of oral tolerance
malfunction
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IDO inhibition significantly affects the ability of CD103+ denxritic cells to promote conversion of naive T cells into Foxp3+Tregs while the ability of CD103- cells is unaffected. IDO inhibition impinges on the development of oral tolerance
malfunction
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the attenuation of Francisella novicida tryptophan mutant bacteria is rescued in the lungs of IDO1-deficient mice
malfunction
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hemodialysis patients characterized by impaired adaptive immunity, exhibit increased IDO expression, further enhanced in the non-responders to hepatitis B virus vaccination
malfunction
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IDO1 pharmacological inhibition causes the rejection of mouse allogeneic concepti, mediated by T cells, and its expression in tumors is associated with their immune evasion. Deletion of IDO1 genomic sequences has the potential to also impact on IDO2 expression due to the chromosomal proximity of the genes, transcription of the IDO2 gene is reduced in the liver of IDO1-/- mice, although protein levels appear to be maintained
malfunction
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the kynurenine pathway is over-activated in Alzheimer's disease mice
metabolism
IDO catalyzes the initial and rate-limiting step in the catabolism of tryptophan along the kynurenine pathway
metabolism
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IDO is a key enzyme that catalyzes the initial, rate-limiting step in tryptophan degradation
metabolism
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IDO is the first and rate-limiting enzyme in the kynurenine pathway
metabolism
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tryptophan 2,3-dioxygenase is an essential enzyme in the pathway of NAD biosynthesis
metabolism
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indoleamine 2,3-dioxygenase catalyses the initial rate-limiting step of tryptophan degradation along the kynurenine pathway
metabolism
indoleamine 2,3-dioxygenase catalyzes the first step in tryptophan breakdown along the kynurenine pathway
metabolism
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three enzymes are now known to catalyze the first and rate-limiting step in the catabolism of tryptophan along the kynurenine pathway: tryptophan 2,3-dioxygenase, indoleamine 2,3-dioxygenase subsequently and a third enzyme, indoleamine 2,3-dioxygenase 2. The kynurenine pathway is a major route for NAD+ synthesis. The pathway is implicated in many disorders and/or their complications, including cerebral malaria, neurological and neurodegenerative diseases
metabolism
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three enzymes are now known to catalyze the first and rate-limiting step in the catabolism of tryptophan along the kynurenine pathway: tryptophan 2,3-dioxygenase, indoleamine 2,3-dioxygenase subsequently and a third enzyme, indoleamine 2,3-dioxygenase 2. The kynurenine pathway is a major route for NAD+ synthesis. The pathway is implicated in many disorders and/or their complications, including cerebral malaria, neurological and neurodegenerative diseases
metabolism
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tryptophan 2,3 dioxygenase is the key regulatory enzyme of the kynurenine pathway
metabolism
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tryptophan 2,3 dioxygenase is the key regulatory enzyme of the kynurenine pathway
metabolism
tryptophan 2,3-dioxygenase catalyzes the oxidative cleavage of the indole ring of L-tryptophan to N-formylkynurenine in the kynurenine pathway
metabolism
comparison of contribution percentage of tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) and indoleamine 2,3-dioxygenase (IDO) to the conversion of L-tryptophan, the calculated percentage conversions indicats that TDO and IDO oxidize 70% and 30%, respectively, of the dietary L-tryptophan. The amount of D-Trp converted to nicotinamide via indole-3-pyruvic acid (IPA) is very low, this amount of D-Trp is converted to L-Trp, which is primarily used for protein synthesis rather than catabolism via the Kyn biosynthesis pathway in mice
metabolism
indoleamine 2,3-dioxygenase-2 (IDO2) is one of three enzymes, alongside tryptophan 2,3-dioxygenase (EC 1.13.11.11) and indoleamine 2,3-dioxygenase (IDO1), that catalyse dioxygenation of L-tryptophan as the first step in the kynurenine pathway
metabolism
the first and rate limiting step of the kynurenine pathway is carried out by two heme-containing enzymes, tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) and indoleamine 2,3-dioxygenase (IDO), which differ in their tissue distribution and regulation
metabolism
the initial and rate-limiting step of the kynurenine pathway involves oxidation of L-Trp toN-formylkynurenine. This is an O2-dependent process and catalyzed by indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase, EC 1.13.11.11
metabolism
infection of THP-1 cells with GRA15-intact Toxoplasma gondii produces IL-1beta in a manner dependent on NLRP3 and caspase-1. This leads to an indirect reduction in IDO1 proteins, thereby supporting parasite growth in human cells
metabolism
overexpression of indoleamine 2,3-dioxygenase in tumor microenvironment results in tumor immune escape
metabolism
the enzyme catalyzes the rate limiting step in the kynurenine pathway of tryptophan metabolism, which is involved in immunity, neuronal function, and aging
metabolism
the enzyme is a tumour cell survival factor that causes immune escape in several types of cancer
metabolism
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comparison of contribution percentage of tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) and indoleamine 2,3-dioxygenase (IDO) to the conversion of L-tryptophan, the calculated percentage conversions indicats that TDO and IDO oxidize 70% and 30%, respectively, of the dietary L-tryptophan. The amount of D-Trp converted to nicotinamide via indole-3-pyruvic acid (IPA) is very low, this amount of D-Trp is converted to L-Trp, which is primarily used for protein synthesis rather than catabolism via the Kyn biosynthesis pathway in mice
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physiological function
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activation of IDO is a key event in the switch from sickness to depression, activation of the innate immune system in the brain is sufficient to activate IDO and to induce depressive-like behavior in the absence of detectable interferon-gamma
physiological function
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IDO inhibits lymphocyte proliferation induced by lectins
physiological function
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IDO is a mechanism for Kupffer cells to induce immune tolerance
physiological function
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IDO is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in normal and pathological settings. IDO5-specific T cells are specifically able to kill IDO-expressing cells. IDO-specific T cells boost viral immunity
physiological function
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IDO is central in the regulation of immune responses
physiological function
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IDO is involved in the maintenance of immune tolerance at the maternal-fetal interface
physiological function
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IDO-1 is one of the key players involved in the pathogenesis of Alzheimer's disease
physiological function
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IDO-expressing skin substitutes significantly suppress T cell infiltration and improve neovascularization by 4fold
physiological function
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indoleamine 2,3-dioxygenase 1 is a lung-specific innate immune defense mechanism that inhibits growth of Francisella tularensis tryptophan auxotrophs
physiological function
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indoleamine 2,3-dioxygenase activity is implicated in the promotion of tolerance to tumors and in autoimmune and inflammatory conditions, itplays a role in arthritis, ischemia-reperfusion injury, haemostatic system, sepsis, atherosclerosis, diabetes, and gut, allergy, and airway inflammation
physiological function
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indoleamine 2,3-dioxygenase is an enzyme involved in tryptophan catabolism with immunosuppressive effects influencing T regulatory/T effector cell balance and oral tolerance induction
physiological function
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indoleamine 2,3-dioxygenase is an enzyme involved in tryptophan catabolism with immunosuppressive effects influencing T regulatory/T effector cell balance and oral tolerance induction
physiological function
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indoleamine 2,3-dioxygenase is critical for regulating immune responses and suppression of inflammation. In human chronic granulomatous disease, IDO metabolic activity is intact
physiological function
indoleamine 2,3-dioxygenase mediates the antiviral effect of interferon-gamma against hepatitis B virus in human hepatocyte-derived cells, indoleamine 2,3-dioxygenase efficiently reduces the level of intracellular hepatitis B virus DNA without altering the steady-state level of viral RNA
physiological function
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TDO expression distinguishes stem cells from more differentiated cells among the granule cells of the adult mouse dentate gyrus. TDO is required at a late-stage of granule cell development, such as during axonal and dendritic growth, synaptogenesis and its maturation
physiological function
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the induction of IDO by interferon-gamma in HLE-B3 cells causes increases in intracellular reactive oxygen species, cytosolic cytochrome c and caspase-3 activity, along with a decrease in protein-free thiol content, are accompanied by apoptosis. IDO-mediated kynurenine formation plays a role in cataract formation related to chronic inflammation
physiological function
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heme enzyme indoleamine 2,3-dioxygenase is a key regulator of immune responses through catalyzing L-tryptophan oxidation. Peroxidase-mediated dioxygenase inactivation, NO consumption, or protein nitration may modulate the biological actions of IDO expressed in inflammatory tissues where the levels of H2O2 and NO are elevated and L-Trp is low
physiological function
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immune regulatory effects of Ido1 and ability of nitric oxide to regulate Ido1 activity, Ido1-mediated metabolism of tryptophan to kynurenine can modulate vascular tone After transient cerebral ischaemia induction in wild-type and Ido1 gene-deficient (Ido1-/-) mice, cerebral ischaemia-reperfusion in wild-type mice increases Ido activity and its expression in cerebral arterioles, while Ido1-/- and 1-methyl-D-tryptophan-treated wild-type mice have lower Ido activity but similar post-stroke neurological function and similar total brain infarct volume and swelling, relative to control mice. Ido1 expression does not appear to affect overall outcome following acute ischaemic stroke
physiological function
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in mammals, IDO1 acts as a defence molecule in combating bacterial and viral infections, as its expression is up-regulated by cytokines such as IFN-gamma, leading to local depletion of L-Trp and causing inhibition of pathogen growth
physiological function
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in mammals, IDO1 acts as a defence molecule in combating bacterial and viral infections, as its expression is up-regulated by cytokines such as IFN-gamma, leading to local depletion of L-Trp and causing inhibition of pathogen growth. IDO2 mRNA is also upregulated in the brain of mice infected with Toxoplasma gondii, an infection in which IFN-gamma driven responses play an important role in controlling parasite growth
physiological function
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indoleamine 2,3-dioxygenase suppresses adaptive immunity. It induces T-cell differentiation to regulatory T-cells through tryptophan depletion and/or kynurenine pathway products. The enzyme decreases glucose uptake by stimulated lymphocytes, increases mitochondrial function in stimulated lymphocytes, decreases aerobic glycolysis in stimulated lymphocytes, and induces the production of the immunosuppressive cytokine IL-10 by stimulated lymphocytes. Effect of IDO on glucose metabolism of lymphocytes, overview
physiological function
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the enzyme is responsible for L-Trp processing that ultimately leads to the biosynthesis of NAD+ and NADP+
physiological function
indoleamine 2,3-dioxygenase depletes tryptophan, activates general control non-derepressible 2 kinase and down-regulates key enzymes involved in fatty acid synthesis in primary human CD4+ T cells. Indoleamine 2,3-dioxygenase is expressed in antigen-presenting cells and exerts immunosuppressive effects on CD4+ T cells through the inhibition of aerobic glycolysis or through downregulation of key enzymes that directly or indirectly promote fatty acid synthesis, a prerequisite for CD4+ T-cell proliferation and differentiation into effector cell lineages. IDO activates GCN2 kinase which inhibits CD4+ T-cell proliferation
physiological function
indoleamine 2,3-dioxygenase, by degrading L-tryptophan, enhances carnitine palmitoyltransferase I activity and fatty acid oxidation, and exerts fatty acid-dependent effects in human alloreactive CD4+ T-cells. The enzyme has an immunoregulatory role in various models of autoimmunity and allotransplantation. IDO increases fatty acid oxidation in mixed lymphocyte reactions and CPT1 enzymatic activity in mixed lymphocyte reaction-derived CD4+ T-cells. IDO decreases ACC2 expression, whereas it increases the level of phosphorylated ACC2 in mixed lymphocyte reaction-derived CD4+ T-cells. IDO increases L-tryptophan degradation in mixed lymphocyte reactions enhances eIF2alpha phosphorylation and CYP1A1 expression in mixed lymphocyte reaction-derived CD4+ T-cells, but does not affect p70S6K phosphorylation in mixed lymphocyte reaction-derived CD4+ T-cells
physiological function
the cytokine-inducible extrahepatic human indoleamine 2,3-dioxygenase (hIDO1) catalyzes the first step of the kynurenine pathway. Immunosuppressive activity of hIDO1 in tumor cells weakens host T-cell immunity, contributing to the progression of cancer
physiological function
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the enzyme catalyses the first and rate-limiting step in the metabolism of L-tryptophan. Degradation of L-Trp leads to the production of several immunosuppressive metabolites, including N-formyl kynurenine and kynurenine. Enzyme IDO-1 also plays a crucial role in immune suppression and tumour induced tolerance. IDO-1 acts as an inducible negative regulator of T cell viability, proliferation and activation
physiological function
the enzyme catalyzes the first and rate-limiting step in the degradation of L-tryptophan, has an important immunomodulatory function. The activity of IDO1 increases in various inflammatory diseases, including tumors, autoimmune diseases, and different kinds of inflammation
physiological function
the enzyme IDO2 might have an immunomodulatory role unrelated to that of IDO1
physiological function
the enzyme is involved in L-tryptophan catabolism to produce bioactive metabolites including kynurenine, kynurenic acid, quinolinic acid, and the coenzyme NAD+ via the kynurenine pathway
physiological function
the enzyme is involved in nicotinamide biosynthesis. Comparison of contribution percentage of tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) and indoleamine 2,3-dioxygenase (IDO) to the conversion of L-tryptophan, the calculated percentage conversions indicats that TDO and IDO oxidize 70% and 30%, respectively, of the dietary L-tryptophan. The amount of D-Trp converted to nicotinamide via indole-3-pyruvic acid (IPA) is very low, this amount of D-Trp is converted to L-Trp, which is primarily used for protein synthesis rather than catabolism via the Kyn biosynthesis pathway in mice
physiological function
the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) suppresses T-cell responses and promotes immune tolerance in tumor resistance, indoleamine 2,3-dioxygenase regulates T cell activity through Vav1/Rac pathway, the inhibitory effects of IDO on T cell immune responses may occur through the downregulation of Vav1 protein expression and the suppression of Vav1/Rac cascade . Enzyme IDO cannot downregulate the expression of the two early signal transductions, namely, ZAP-70 and CD3lambda
physiological function
conversion of tryptophan to N-formylkynurenine is the first and rate-limiting step of the tryptophan metabolic pathway (i.e., the kynurenine pathway). This conversion is catalyzed by three enzyme isoforms: indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan-2,3-dioxygenase (TDO)
physiological function
IFN-gamma stimulates the expression of indoleamine 2,3-dioxygenase to degrade tryptophan, an essential nutritional amino acid for the intracellular growth of Toxoplasma gondii in human cells
physiological function
in the tryptophan-nicotinamide pathway, indoleamine 2,3-dioxygenase 1 (IDO1) participates in the first step and catalyzes the formation of N-formylkynurnine by promoting the oxidative cleavage of indole 2,3-double bonds
physiological function
key enzyme in degradation of tryptophan into immunosuppressive kynurenine
physiological function
the enzyme catalyses the rate-limiting step in the kynurenine pathway, an important biochemical mechanism for immunological responsecancers express tryptophan catabolising enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2) to produce immunosuppressive tryptophan metabolites that undermine thr immune systems of patients, leading to poor disease outcomes
physiological function
the enzyme catalyzes the rate limiting step in the kynurenine pathway of tryptophan metabolism, which is involved in immunity, neuronal function, and aging
physiological function
the enzyme is overactivated or overexpressed in many human cancers, which is associated with poor patient outcomes
physiological function
the enzyme plays a crucial role in immune tolerance
physiological function
the enzyme plays an important role in the immune escape of tumors
physiological function
the enzyme plays multiple roles in the immunity of fish
physiological function
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the enzyme is involved in nicotinamide biosynthesis. Comparison of contribution percentage of tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) and indoleamine 2,3-dioxygenase (IDO) to the conversion of L-tryptophan, the calculated percentage conversions indicats that TDO and IDO oxidize 70% and 30%, respectively, of the dietary L-tryptophan. The amount of D-Trp converted to nicotinamide via indole-3-pyruvic acid (IPA) is very low, this amount of D-Trp is converted to L-Trp, which is primarily used for protein synthesis rather than catabolism via the Kyn biosynthesis pathway in mice
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additional information
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H2O2 activates the peroxidase function to induce protein oxidation and inhibit dioxygenase activity, overview. Dioxygenase inhibition correlated with IDO-catalyzed H2O2 consumption, compound I-mediated formation of protein-centered radicals, altered protein secondary structure, and opening of the distal heme pocket to promote nonproductive substrate binding, inhibited by L-Trp, the heme ligand cyanide, or free radical scavengers
additional information
F5H5G0
IDO1 and IDO2 have different kinetic parameters and different inhibition profiles
additional information
IDO1 and IDO2 have different kinetic parameters and different inhibition profiles
additional information
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IDO1 and IDO2 have different kinetic parameters and different inhibition profiles
additional information
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molecular dynamics simulation studies, overview. Structural role of T342 in controlling the substrate stereoselectivity of the enzyme
additional information
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transcription of the IDO2 gene is complex. IDO1 expression is found in most tissues and is regulated by immunological signals, including interferon-gamma, lipopolysaccharide and tumor necrosis factor
additional information
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transcription of the IDO2 gene is complex. IDO1 expression is found in most tissues and is regulated by immunological signals, including interferon-gamma, lipopolysaccharide and tumor necrosis factor
additional information
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Xanthomonas campestris TDO shows an H-bond between T254 and the ammonium group of the substrate is present in the L-Trp-bound enzyme, but not in the D-Trp bound enzyme, molecular dynamics simulation studies. T254 controls the substrate stereoselectivity of the enzyme by modulating the H-bonding interaction between the NH3-group and epoxide oxygen of the ferryl/indole 2,3-epoxide intermediate of the enzyme, and regulating the dynamics of two active site loops, loop250-260 and loop117-130, critical for substrate-binding, O2 and L-trp both are bound in the active site
additional information
active site-inhibitor interactions, overview. Importance of the Ser167 and the Cys129 residues in the IDO1 active site
additional information
conformational dynamics in three-dimensional structure of hIDO, and structure-function analysis, modeling using structures PDB IDs 2D0T, 2NW8, and 2X67, overview. Flexible active site loop in human indoleamine 2,3-dioxygenase
additional information
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conformational dynamics in three-dimensional structure of hIDO, and structure-function analysis, modeling using structures PDB IDs 2D0T, 2NW8, and 2X67, overview. Flexible active site loop in human indoleamine 2,3-dioxygenase
additional information
human indoleamine 2,3-dioxygenase-2 substrate specificity and inhibition characteristics are distinct from those of indoleamine 2,3-dioxygenase-1
additional information
human indoleamine 2,3-dioxygenase-2 substrate specificity and inhibition characteristics are distinct from those of indoleamine 2,3-dioxygenase-1
additional information
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human indoleamine 2,3-dioxygenase-2 substrate specificity and inhibition characteristics are distinct from those of indoleamine 2,3-dioxygenase-1
additional information
IDO homology modeling, overview
additional information
important amino acid residues that stabilize the substrate in the active site: a cluster of small side chain residues at positions 260-265 ensures structural flexibility of the binding site. Thr379 and Arg231 are key residues acting in concert to bind the substrate. Thr379 is the final residue of a disordered loop, the neighboring Gly380 is 20 A away from the heme iron. Residues Ser167, Phe226, Phe227, and Arg231 may play critical roles. Stucture-function analysis by spectrocopic methods, overview. The hIDO1 distal heme pocket is in part lined by a sequence of residues with small side chains (residues 260-265: AGGSAG) rendering structural flexibility to the active site, which may be required to accommodate the substrate
additional information
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important amino acid residues that stabilize the substrate in the active site: a cluster of small side chain residues at positions 260-265 ensures structural flexibility of the binding site. Thr379 and Arg231 are key residues acting in concert to bind the substrate. Thr379 is the final residue of a disordered loop, the neighboring Gly380 is 20 A away from the heme iron. Residues Ser167, Phe226, Phe227, and Arg231 may play critical roles. Stucture-function analysis by spectrocopic methods, overview. The hIDO1 distal heme pocket is in part lined by a sequence of residues with small side chains (residues 260-265: AGGSAG) rendering structural flexibility to the active site, which may be required to accommodate the substrate