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Tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase

Abstract:

Maintaining stable tryptophan levels is required to control neuronal and immune activity. We report that tryptophan homeostasis is largely controlled by the stability of tryptophan 2,3-dioxygenase (TDO), the hepatic enzyme responsible for tryptophan catabolism. High tryptophan levels stabilize the active tetrameric conformation of TDO through binding noncatalytic exosites, resulting in rapid catabolism of tryptophan. In low tryptophan, the lack of tryptophan binding in the exosites destabiliz...

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Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1073/pnas.2022447118

Authors


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Role:
Author
ORCID:
0000-0003-2285-9177
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Role:
Author
ORCID:
0000-0001-5574-6123
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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Oxford Ludwig Institute
Role:
Author
ORCID:
0000-0001-5641-5019
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Role:
Author
ORCID:
0000-0001-6761-6836
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Publisher:
National Academy of Sciences Publisher's website
Journal:
Proceedings of the National Academy of Sciences of the United States of America Journal website
Volume:
118
Issue:
23
Article number:
e2022447118
Place of publication:
United States
Publication date:
2021-06-01
Acceptance date:
2021-04-02
DOI:
EISSN:
1091-6490
ISSN:
0027-8424
Pmid:
34074763
Language:
English
Keywords:
Pubs id:
1181612
Local pid:
pubs:1181612
Deposit date:
2021-07-14

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