General Stability | Organism |
---|---|
high tryptophan levels stabilize the active tetrameric conformation of the enzyme through binding noncatalytic exosites, resulting in rapid catabolism of tryptophan | Homo sapiens |
in low tryptophan, the lack of tryptophan binding in the exosites destabilizes the tetramer into inactive monomers and dimers | Homo sapiens |
the nonmetabolizable analog alpha-methyl-tryptophan stabilizes tetrameric enzyme and thereby stably reduces tryptophanemia | Homo sapiens |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
48000 | - |
in the absence of tryptophan, inactive monomer, gel filtration | Homo sapiens |
96000 | - |
in the absence of tryptophan, inactive dimer, gel filtration | Homo sapiens |
192000 | - |
in the presence of tryptophan, tetramer, gel filtration | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-tryptophan + O2 | Homo sapiens | - |
N-formyl-L-kynurenine | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P48775 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
ubiquitination | in low tryptophan, the lack of tryptophan binding in the exosites destabilizes the tetramer into inactive monomers and dimers and unmasks a four-amino acid degron that triggers polyubiquitination of tryptophan 2,3-dioxygenase by SKP1-CUL1-F-box complexes, resulting in proteasome-mediated degradation of the enzyme and rapid interruption of tryptophan catabolism | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
A-172 cell | ATCC-CRL-1620 | Homo sapiens | - |
liver | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-tryptophan + O2 | - |
Homo sapiens | N-formyl-L-kynurenine | - |
? |
Subunits | Comment | Organism |
---|---|---|
tetramer | 4 * 48000, high tryptophan levels stabilize the active tetrameric conformation of the enzyme through binding noncatalytic exosites. The lack of tryptophan binding in the exosites destabilizes the tetramer into inactive monomers and dimers | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
TDO | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
physiological function | tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase. A mechanism allows stable tryptophanemia despite varying levels of tryptophan supply in the diet. High tryptophan availability stabilizes tryptophan 2,3-dioxygenase in the liver, allowing efficient tryptophan catabolism. In contrast, low tryptophan levels trigger proteasome-mediated degradation of tryptophan 2,3-dioxygenase, thereby stopping tryptophan catabolism and preventing hypotryptophanemia | Homo sapiens |