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Literature summary for 1.13.11.11 extracted from

  • Klaessens, S.; Stroobant, V.; Hoffmann, D.; Gyrd-Hansen, M.; Pilotte, L.; Vigneron, N.; De Plaen, E.; Van den Eynde, B.J.
    Tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase (2021), Proc. Natl. Acad. Sci. USA, 118, e2022447118 .
    View publication on PubMedView publication on EuropePMC
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General Stability

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 [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/ Products (Substrates)

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

Organism

Organism UniProt Comment Textmining
Homo sapiens P48775
-
-

Posttranslational Modification

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

Source Tissue Comment Organism Textmining
A-172 cell ATCC-CRL-1620 Homo sapiens
-
liver
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-tryptophan + O2
-
 Homo sapiens N-formyl-L-kynurenine
-
 ?

Subunits

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

Synonyms Comment Organism
TDO
-
 Homo sapiens

General Information

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