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Literature summary for 1.13.11.52 extracted from

  • Fatokun, A.A.; Hunt, N.H.; Ball, H.J.
    Indoleamine 2,3-dioxygenase 2 (IDO2) and the kynurenine pathway: characteristics and potential roles in health and disease (2013), Amino Acids, 45, 1319-1329.
    View publication on PubMed

Inhibitors

Inhibitors Comment Organism Structure
1-methyl-D-tryptophan selective inhibition of IDO2, 1DMT is not efficacious in a tumor model on an IDO1-/- background Homo sapiens
1-methyl-D-tryptophan
-
Mus musculus
1-methyl-L-tryptophan better inhibitor of IDO2 enzymatic activity than 1DMT in both cell-free and cellular assays Homo sapiens
1-methyl-L-tryptophan better inhibitor of IDO2 enzymatic activity than 1DMT in both cell-free and cellular assays Mus musculus
4-phenylimidazole an IDO1 inhibitor Mus musculus
L-tryptophan substrate inhibition of IDO1, not of IDO2 Mus musculus
tenatoprazole highly selective for IDO2 inhibition, no inhibition of IDO1 or tryptophan dioxygenase Mus musculus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.028
-
L-tryptophan IDO1, pH and temperature not specified in the publication, MB assay Mus musculus
0.029
-
L-tryptophan IDO1, pH and temperature not specified in the publication, cytochrome b5 assay Mus musculus
0.53
-
L-tryptophan IDO1, pH and temperature not specified in the publication, cytochrome b5 assay Mus musculus
12
-
L-tryptophan IDO1, pH and temperature not specified in the publication, MB assay Mus musculus

Metals/Ions

Metals/Ions Comment Organism Structure
Fe2+ heme-containing enzyme Mus musculus
Fe2+ heme-containing enzyme Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
45000
-
x * 45000, about, IDO2, SDS-PAGE Mus musculus
47000
-
x * 47000, about, IDO2, SDS-PAGE Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
D-tryptophan + O2 Mus musculus IDO1 N-formyl-D-kynurenine
-
?
D-tryptophan + O2 Homo sapiens IDO1 N-formyl-D-kynurenine
-
?
L-tryptophan + O2 Mus musculus IDO1 and IDO2 N-formyl-L-kynurenine
-
?
L-tryptophan + O2 Homo sapiens IDO1 and IDO2 N-formyl-L-kynurenine
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mus musculus
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
brain IDO2 Mus musculus
-
brain IDO2 Homo sapiens
-
epididymis IDO1 is constitutively expressed in the epididymis Mus musculus
-
kidney IDO2 Mus musculus
-
kidney IDO2 Homo sapiens
-
liver IDO2 Mus musculus
-
liver IDO2 Homo sapiens
-
additional information IDO1 expression is found in most tissues and is regulated by immunological signals, including interferon-gamma, lipopolysaccharide and tumor necrosis factor Homo sapiens
-
additional information IDO1 expression is found in most tissues and is regulated by immunological signals, including interferon-gamma, lipopolysaccharide and tumor necrosis factor. Expression of IDO2 protein in the liver and kidney in these IDO1-/- mice is unaffected, although the IDO2 transcript is downregulated. It is possible that the deletion of the IDO1 gene affects the expression of the IDO2 protein in other cell types, and 1DMT's effects might be mediated through either or both IDO isoforms Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
D-tryptophan + O2 IDO1 Mus musculus N-formyl-D-kynurenine
-
?
D-tryptophan + O2 IDO1 Homo sapiens N-formyl-D-kynurenine
-
?
L-tryptophan + O2 IDO1 and IDO2 Mus musculus N-formyl-L-kynurenine
-
?
L-tryptophan + O2 IDO1 and IDO2 Homo sapiens N-formyl-L-kynurenine
-
?

Subunits

Subunits Comment Organism
monomer x * 45000, about, IDO2, SDS-PAGE Mus musculus
monomer x * 47000, about, IDO2, SDS-PAGE Homo sapiens

Synonyms

Synonyms Comment Organism
IDO1
-
Mus musculus
IDO1
-
Homo sapiens
IDO2
-
Mus musculus
IDO2
-
Homo sapiens
indoleamine 2,3-dioxygenase 1
-
Mus musculus
indoleamine 2,3-dioxygenase 1
-
Homo sapiens
indoleamine 2,3-dioxygenase 2
-
Mus musculus
indoleamine 2,3-dioxygenase 2
-
Homo sapiens
indoleamine 2,3-dioxygenase-like protein
-
Mus musculus
indoleamine 2,3-dioxygenase-like protein
-
Homo sapiens

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
48
-
complete denaturation of IDO2, partially of IDO1 Mus musculus
60
-
complete denaturation of IDO1 Mus musculus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
6 6.5 IDO1 Mus musculus
7.4 7.5 IDO2 Mus musculus

Cofactor

Cofactor Comment Organism Structure
heme
-
Mus musculus
heme
-
Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0018
-
tenatoprazole IDO2, pH and temperature not specified in the publication Mus musculus
1.6
-
L-tryptophan inhibition of IDO1, pH and temperature not specified in the publication Mus musculus

Expression

Organism Comment Expression
Homo sapiens IDO1 expression is upregulated by cytokines such as IFN-gamma, e.g. in HELA cells, IDO2 mRNA expression is upregulated in response to IFN-gamma in some cancer cell lines as well and human mesenchymal stem cells up
Mus musculus IDO1 expression is upregulated by cytokines such as IFN-gamma, IDO2 is upregulated in mouse dendritic cell lines as well as mouse mesenchymal stem cells. 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 up

General Information

General Information Comment Organism
malfunction 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 Mus musculus
metabolism 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 Mus musculus
metabolism 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 Homo sapiens
additional information 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 Mus musculus
additional information 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 Homo sapiens
physiological function 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 Homo sapiens
physiological function 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 Mus musculus