Indoleamine 2,3-dioxygenase

Indoleamine 2,3-dioxygenase 1
250px PDB rendering based on 2d0t.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2D0T, 2D0U, 4PK5, 4PK6
Identifiers
Symbols	IDO1 ; IDO; IDO-1; INDO
External IDs	OMIM: 147435 MGI: 96416 HomoloGene: 48082 ChEMBL: 4685 GeneCards: IDO1 Gene
EC number	1.13.11.52
Gene ontology Molecular function • tryptophan 2,3-dioxygenase activity • electron carrier activity • heme binding • indoleamine 2,3-dioxygenase activity • metal ion binding Cellular component • cytosol • smooth muscle contractile fiber • stereocilium bundle Biological process • cytokine production involved in inflammatory response • positive regulation of T cell tolerance induction • positive regulation of chronic inflammatory response • positive regulation of type 2 immune response • tryptophan catabolic process • female pregnancy • tryptophan catabolic process to kynurenine • response to lipopolysaccharide • negative regulation of interleukin-10 production • positive regulation of interleukin-12 production • multicellular organismal response to stress • kynurenic acid biosynthetic process • cellular nitrogen compound metabolic process • swimming behavior • negative regulation of T cell proliferation • small molecule metabolic process • regulation of activated T cell proliferation • oxidation-reduction process • negative regulation of T cell apoptotic process • positive regulation of T cell apoptotic process Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE INDO 210029 at tn.png
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3620	15930
Ensembl	ENSG00000131203	ENSMUSG00000031551
UniProt	P14902	P28776
RefSeq (mRNA)	NM_002164	NM_001293690
RefSeq (protein)	NP_002155	NP_001280619
Location (UCSC)	Chr 8: 39.9 – 39.93 Mb	Chr 8: 24.58 – 24.6 Mb
PubMed search	[1]	[2]

Indoleamine-pyrrole 2,3-dioxygenase (IDO or INDO EC 1.13.11.52) is an enzyme that in humans is encoded by the IDO1 gene. This enzyme catalyzes the degradation of the essential amino acid L-tryptophan to N-formylkynurenine.

Function

Indoleamine 2,3-dioxygenase is the first and rate-limiting enzyme of tryptophan catabolism through kynurenine pathway, thus causing depletion of tryptophan which can cause halted growth of microbes as well as T cells. PGE2 is able to elevate the expression of indoleamine 2,3-dioxygenase in CD11C(+) dendritic cells and promots the development of functional Treg cells.

IDO is an immune checkpoint molecule in the sense that it is an immunomodulatory enzyme produced by some alternatively activated macrophages and other immunoregulatory cells (also used as an immune subversion strategy by many tumors). Interferon-gamma has an antiproliferative effect on many tumor cells and inhibits intracellular pathogens such as Toxoplasma and Chlamydia, at least partly because of the induction of indoleamine 2,3-dioxygenase.

Clinical significance

It has been shown that IDO permits tumor cells to escape the immune system by depletion of L-Trp in the microenvironment of cells. A wide range of human cancers such as prostatic, colorectal, pancreatic, cervical, gastric, ovarian, head, lung, etc. overexpress human IDO (hIDO).

Inhibitors

Norharmane, via inhibition of indoleamine 2,3-dioxygenase exerts neuroprotective properties by suppressing kynurenine neurotoxic metabolites such as quinolinic acid, 3-hydroxy-kynurenine and nitric oxide synthase. Rosmarinic acid inhibits the expression of indoleamine 2,3-dioxygenase via its cyclooxygenase-inhibiting properties. COX-2 inhibitors down-regulate indoleamine 2,3-dioxygenase, leading to a reduction in kynurenine levels as well as reducing proinflammatory cytokine activity. Alpha-methyl-tryptophan also inhibits indoleamine dioxygenase.

Indoleamine 2,3-dioxygenase File:PDB 2d0t EBI.jpg crystal structure of 4-phenylimidazole bound form of human indoleamine 2,3-dioxygenase Identifiers Symbol IDO Pfam PF01231 Pfam clan CL0380 InterPro IPR000898 PROSITE PDOC00684 Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Indoleamine 2,3-dioxygenase Identifiers EC number 1.13.11.52 CAS number Template:CAS Databases IntEnz IntEnz view BRENDA BRENDA entry ExPASy NiceZyme view KEGG KEGG entry MetaCyc metabolic pathway PRIAM profile PDB structures RCSB PDB PDBe PDBsum Gene Ontology AmiGO / EGO Search PMC articles PubMed articles NCBI proteins

See also

• 1-Methyltryptophan
• Tryptophan 2,3-dioxygenase

External links

• Indoleamine-Pyrrole 2,3,-Dioxygenase at the US National Library of Medicine Medical Subject Headings (MeSH)