Summary: Indoleamine 2,3-dioxygenase
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Indoleamine 2,3-dioxygenase Edit Wikipedia article
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.[1][2] This enzyme catalyzes the degradation of the essential amino acid L-tryptophan to N-formylkynurenine.[3]
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[edit] 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.
INDO is an immunomodulatory enzyme produced by some alternatively activated macrophages and other immunoregulatory cells (also used as an immune subversion strategy by many tumors). INDO 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.
[edit] 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.[4] Rosmarinic acid inhibits the expression of indoleamine 2,3-dioxygenase via its cyclooxygenase-inhibiting properties.[5] COX-2 inhibitors down-regulate indoleamine 2,3-dioxygenase, leading to a reduction in kynurenine levels as well as reducing proinflammatory cytokine activity.[6]
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[edit] See also
[edit] References
- ^ Dai W, Gupta SL (April 1990). "Molecular cloning, sequencing and expression of human interferon-gamma-inducible indoleamine 2,3-dioxygenase cDNA". Biochem. Biophys. Res. Commun. 168 (1): 1â8. doi:10.1016/0006-291X(90)91666-G. PMID 2109605.
- ^ Najfeld V, Menninger J, Muhleman D, Comings DE, Gupta SL (1993). "Localization of indoleamine 2,3-dioxygenase gene (INDO) to chromosome 8p12-->p11 by fluorescent in situ hybridization". Cytogenet. Cell Genet. 64 (3â4): 231â2. doi:10.1159/000133584. PMID 8404046.
- ^ "Entrez Gene: INDO indoleamine-pyrrole 2,3 dioxygenase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3620.
- ^ Chiarugi A, Dello Sbarba P, Paccagnini A, Donnini S, Filippi S, Moroni F (August 2000). "Combined inhibition of indoleamine 2,3-dioxygenase and nitric oxide synthase modulates neurotoxin release by interferon-gamma-activated macrophages". J. Leukoc. Biol. 68 (2): 260â6. PMID 10947071. http://www.jleukbio.org/content/68/2/260.long.
- ^ Lee HJ, Jeong YI, Lee TH, et al. (May 2007). "Rosmarinic acid inhibits indoleamine 2,3-dioxygenase expression in murine dendritic cells". Biochem. Pharmacol. 73 (9): 1412â21. doi:10.1016/j.bcp.2006.12.018. PMID 17229401.
- ^ Cesario A, Rocca B, Rutella S (2011). "The interplay between indoleamine 2,3-dioxygenase 1 (IDO1) and cyclooxygenase (COX)-2 in chronic inflammation and cancer". Curr. Med. Chem. 18 (15): 2263â71. PMID 21517752.
[edit] Further reading
- Grohmann U, Fallarino F, Puccetti P (2004). "Tolerance, DCs and tryptophan: much ado about IDO". Trends Immunol. 24 (5): 242â8. doi:10.1016/S1471-4906(03)00072-3. PMID 12738417.
- Takikawa O (2005). "Biochemical and medical aspects of the indoleamine 2,3-dioxygenase-initiated L-tryptophan metabolism". Biochem. Biophys. Res. Commun. 338 (1): 12â9. doi:10.1016/j.bbrc.2005.09.032. PMID 16176799.
- Puccetti P (2007). "On watching the watchers: IDO and type I/II IFN". Eur. J. Immunol. 37 (4): 876â9. doi:10.1002/eji.200737184. PMID 17393386.
- Kadoya A, Tone S, Maeda H, et al. (1992). "Gene structure of human indoleamine 2,3-dioxygenase". Biochem. Biophys. Res. Commun. 189 (1): 530â6. doi:10.1016/0006-291X(92)91590-M. PMID 1449503.
- Kamimura S, Eguchi K, Yonezawa M, Sekiba K (1991). "Localization and developmental change of indoleamine 2,3-dioxygenase activity in the human placenta". Acta Med. Okayama 45 (3): 135â9. PMID 1716396.
- Tone S, Takikawa O, Habara-Ohkubo A, et al. (1990). "Primary structure of human indoleamine 2,3-dioxygenase deduced from the nucleotide sequence of its cDNA". Nucleic Acids Res. 18 (2): 367. doi:10.1093/nar/18.2.367. PMC 330282. PMID 2326172. //www.ncbi.nlm.nih.gov/pmc/articles/PMC330282/.
- Werner-Felmayer G, Werner ER, Fuchs D, et al. (1990). "Tumour necrosis factor-alpha and lipopolysaccharide enhance interferon-induced tryptophan degradation and pteridine synthesis in human cells". Biol. Chem. Hoppe-Seyler 370 (9): 1063â9. PMID 2482041.
- Carlin JM, Borden EC, Byrne GI (1989). "Interferon-induced indoleamine 2,3-dioxygenase activity inhibits Chlamydia psittaci replication in human macrophages". J. Interferon Res. 9 (3): 329â37. doi:10.1089/jir.1989.9.329. PMID 2501398.
- Kobayashi K, Hayashi K, Sono M (1989). "Effects of tryptophan and pH on the kinetics of superoxide radical binding to indoleamine 2,3-dioxygenase studied by pulse radiolysis". J. Biol. Chem. 264 (26): 15280â3. PMID 2549057.
- Daley-Yates PT, Powell AP, Smith LL (1989). "Pulmonary indoleamine 2,3-dioxygenase activity and its significance in the response of rats, mice, and rabbits to oxidative stress". Toxicol. Appl. Pharmacol. 96 (2): 222â32. doi:10.1016/0041-008X(88)90082-8. PMID 2848333.
- Burkin DJ, Kimbro KS, Barr BL, et al. (1993). "Localization of the human indoleamine 2,3-dioxygenase (IDO) gene to the pericentromeric region of human chromosome 8". Genomics 17 (1): 262â3. doi:10.1006/geno.1993.1319. PMID 8406467.
- Malina HZ, Martin XD (1996). "Indoleamine 2,3-dioxygenase: antioxidant enzyme in the human eye". Graefes Arch. Clin. Exp. Ophthalmol. 234 (7): 457â62. doi:10.1007/BF02539413. PMID 8817290.
- Munn DH, Zhou M, Attwood JT, et al. (1998). "Prevention of allogeneic fetal rejection by tryptophan catabolism". Science 281 (5380): 1191â3. doi:10.1126/science.281.5380.1191. PMID 9712583.
- Takikawa O, Littlejohn TK, Truscott RJ (2001). "Indoleamine 2,3-dioxygenase in the human lens, the first enzyme in the synthesis of UV filters". Exp. Eye Res. 72 (3): 271â7. doi:10.1006/exer.2000.0951. PMID 11180976.
- Kudo Y, Boyd CA (2001). "The role of l-tryptophan transport in l-tryptophan degradation by indoleamine 2,3-dioxygenase in human placental explants". J. Physiol. (Lond.) 531 (Pt 2): 417â23. doi:10.1111/j.1469-7793.2001.0417i.x. PMC 2278460. PMID 11230514. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2278460/.
- Terentis AC, Thomas SR, Takikawa O, et al. (2002). "The heme environment of recombinant human indoleamine 2,3-dioxygenase. Structural properties and substrate-ligand interactions". J. Biol. Chem. 277 (18): 15788â94. doi:10.1074/jbc.M200457200. PMID 11867636.
- Kvirkvelia N, Vojnovic I, Warner TD, et al. (2002). "Placentally derived prostaglandin E2 acts via the EP4 receptor to inhibit IL-2-dependent proliferation of CTLL-2 T cells". Clin. Exp. Immunol. 127 (2): 263â9. doi:10.1046/j.1365-2249.2002.01718.x. PMC 1906325. PMID 11876748. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1906325/.
- Sedlmayr P, Blaschitz A, Wintersteiger R, et al. (2002). "Localization of indoleamine 2,3-dioxygenase in human female reproductive organs and the placenta". Mol. Hum. Reprod. 8 (4): 385â91. doi:10.1093/molehr/8.4.385. PMID 11912287.
[edit] External links
- Indoleamine-Pyrrole 2,3,-Dioxygenase at the US National Library of Medicine Medical Subject Headings (MeSH)
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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Indoleamine 2,3-dioxygenase Provide feedback
No Pfam abstract.
Internal database links
| Similarity to PfamA using HHSearch: | DUF1864 |
External database links
| PANDIT: | PF01231 |
| PROSITE: | PDOC00684 |
| Pseudofam: | PF01231 |
| SYSTERS: | IDO |
This tab holds annotation information from the InterPro database.
InterPro entry IPR000898
Indoleamine 2,3-dioxgyenase (IDO, EC) [PUBMED:1907934] is a cytosolic haem protein which, together with the hepatic enzyme tryptophan 2,3-dioxygenase, catalyzes the conversion of tryptophan and other indole derivatives to kynurenines. The physiological role of IDO is not fully understood but is of great interest, because IDO is widely distributed in human tissues, can be up-regulated via cytokines such as interferon-gamma, and can thereby modulate the levels of tryptophan, which is vital for cell growth. The degradative action of IDO on tryptophan leads to cell death by starvation of this essential and relatively scarce amino acid. IDO is a haem-containing enzyme of about 400 amino acids. Site-directed mutagenesis showed His346 (SWISSPROT) to be essential for haem binding, indicating that this histidine residue may be the proximal ligand. Mutation of Asp274 also compromised the ability of IDO to bind haem, suggesting that Asp274 may coordinate to haem directly as the distal ligand or is essential in maintaining the conformation of the haem pocket [PUBMED:12766158].
Other proteins that are evolutionarily related to IDO include yeast hypothetical protein YJR078w; and myoglobin from the red muscle of the archaeogastropodic molluscs, Nordotis madaka (Giant abalone) and Sulculus diversicolor [PUBMED:8011076, PUBMED:12711393]. These unusual globins lack enzymatic activity but have kept the haem group.
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Molecular function | heme binding (GO:0020037) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan IDO-like (CL0380), which contains the following 3 members:
DUF1864 IDO Trp_dioxygenaseAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...
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| Seed (39) |
Full (516) |
Representative proteomes | NCBI (501) |
Meta (538) |
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| RP15 (115) |
RP35 (201) |
RP55 (288) |
RP75 (368) |
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| PP/heatmap | 1 | |||||||
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| Seed (39) |
Full (516) |
Representative proteomes | NCBI (501) |
Meta (538) |
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|---|---|---|---|---|---|---|---|---|
| RP15 (115) |
RP35 (201) |
RP55 (288) |
RP75 (368) |
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| Raw Stockholm | ||||||||
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
External links
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Prosite |
| Previous IDs: | none |
| Type: | Family |
| Author: | Finn RD, Bateman A |
| Number in seed: | 39 |
| Number in full: | 516 |
| Average length of the domain: | 358.10 aa |
| Average identity of full alignment: | 28 % |
| Average coverage of the sequence by the domain: | 79.96 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 423 | ||||||||||||
| Family (HMM) version: | 13 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Interactions
There is 1 interaction for this family. More...
IDOStructures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the IDO domain has been found. There are 4 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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Archea
Eukaryota
Bacteria
Other sequences
Viruses
Unclassified
Viroids
Unclassified sequence