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MetaCyc Enzyme: indoleamine 2,3-dioxygenase

Gene: INDO Accession Number: G-11449 (MetaCyc)

Synonyms: IDO, IDO1

Species: Homo sapiens

Summary:
The apparent molecular mass of the enzyme was determined by SDS-PAGE [Littlejohn03] . In mammals this monomeric enzyme is present in most tissues with the exception of liver, which contains tryptophan 2,3-dioxygenase. Catalytic differences between these two enzymes have been shown [Basran08]. The enzyme has been reviewed in [Rafice09] and [King07].

Recombinant enzyme has been cloned, expressed in Saccharomyces cerevisiae [Vottero06] and Escherichia coli, [Littlejohn03] and purified. Differences between the recombinant human and mouse enzymes have been studied [Austin09].

The crystal structure of this enzyme has been determined [Sugimoto06].

A third enzyme indoleamine 2,3-dioxygenase-2 has been described in mouse. It is expressed in liver, kidney and in the reproductive system. It differs from this enzyme in its selectivity for some inhibitors. Its biological function remains to be determined [Ball09].

Gene Citations: [Dai90, Tone90, Kadoya92]

Map Position: [39,771,328 -> 39,785,950]

Molecular Weight of Polypeptide: 45.326 kD (from nucleotide sequence), 45.0 kD (experimental)

Unification Links: ArrayExpress:P14902 , Entrez-gene:3620 , Mint:MINT-1414454 , PhosphoSite:P14902 , Pride:P14902 , Protein Model Portal:P14902 , SMR:P14902 , String:9606.ENSP00000253513 , UniProt:P14902

Relationship Links: InterPro:IN-FAMILY:IPR000898 , PDB:Structure:2D0T , PDB:Structure:2D0U , Pfam:IN-FAMILY:PF01231 , Prosite:IN-FAMILY:PS00876 , Prosite:IN-FAMILY:PS00877

Gene-Reaction Schematic: ?


Enzymatic reaction of: indoleamine 2,3-dioxygenase

Synonyms: indoleamine-pyrrole 2,3-dioxygenase

EC Number: 1.13.11.11

L-tryptophan + oxygen <=> N-formylkynurenine

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

Alternative Substrates for L-tryptophan: D-tryptophan [Littlejohn03 ] , 5-hydroxy-L-tryptophan [Littlejohn03 ]

In Pathways: tryptophan degradation III (eukaryotic) , tryptophan degradation XI (mammalian, via kynurenine) , NAD biosynthesis II (from tryptophan) , tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde

Summary:
This enzyme catalyzes the oxidative cleavage of the 2-3 double bond in L-tryptophan, producing N-formylkynurenine (in [Littlejohn03]).

Cofactors or Prosthetic Groups: heme b [Rafice09]

Kinetic Parameters:

Substrate
Km (μM)
Citations
L-tryptophan
20.0
[Littlejohn03]


References

Austin09: Austin CJ, Astelbauer F, Kosim-Satyaputra P, Ball HJ, Willows RD, Jamie JF, Hunt NH (2009). "Mouse and human indoleamine 2,3-dioxygenase display some distinct biochemical and structural properties." Amino Acids 36(1);99-106. PMID: 18274832

Ball09: Ball HJ, Yuasa HJ, Austin CJ, Weiser S, Hunt NH (2009). "Indoleamine 2,3-dioxygenase-2; a new enzyme in the kynurenine pathway." Int J Biochem Cell Biol 41(3);467-71. PMID: 18282734

Basran08: Basran J, Rafice SA, Chauhan N, Efimov I, Cheesman MR, Ghamsari L, Raven EL (2008). "A kinetic, spectroscopic, and redox study of human tryptophan 2,3-dioxygenase." Biochemistry 47(16);4752-60. PMID: 18370401

Dai90: Dai W, Gupta SL (1990). "Molecular cloning, sequencing and expression of human interferon-gamma-inducible indoleamine 2,3-dioxygenase cDNA." Biochem Biophys Res Commun 168(1);1-8. PMID: 2109605

Kadoya92: Kadoya A, Tone S, Maeda H, Minatogawa Y, Kido R (1992). "Gene structure of human indoleamine 2,3-dioxygenase." Biochem Biophys Res Commun 189(1);530-6. PMID: 1449503

King07: King NJ, Thomas SR (2007). "Molecules in focus: indoleamine 2,3-dioxygenase." Int J Biochem Cell Biol 39(12);2167-72. PMID: 17320464

Littlejohn03: Littlejohn TK, Takikawa O, Truscott RJ, Walker MJ (2003). "Asp274 and his346 are essential for heme binding and catalytic function of human indoleamine 2,3-dioxygenase." J Biol Chem 278(32);29525-31. PMID: 12766158

Rafice09: Rafice SA, Chauhan N, Efimov I, Basran J, Raven EL (2009). "Oxidation of L-tryptophan in biology: a comparison between tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase." Biochem Soc Trans 37(Pt 2);408-12. PMID: 19290871

Sugimoto06: Sugimoto H, Oda S, Otsuki T, Hino T, Yoshida T, Shiro Y (2006). "Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase." Proc Natl Acad Sci U S A 103(8);2611-6. PMID: 16477023

Tone90: Tone S, Takikawa O, Habara-Ohkubo A, Kadoya A, Yoshida R, Kido R (1990). "Primary structure of human indoleamine 2,3-dioxygenase deduced from the nucleotide sequence of its cDNA." Nucleic Acids Res 18(2);367. PMID: 2326172

Vottero06: Vottero E, Mitchell DA, Page MJ, MacGillivray RT, Sadowski IJ, Roberge M, Mauk AG (2006). "Cytochrome b(5) is a major reductant in vivo of human indoleamine 2,3-dioxygenase expressed in yeast." FEBS Lett 580(9);2265-8. PMID: 16574111


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Tue Nov 25, 2014, BIOCYC14B.