Structural highlights
Function
T23O_HUMAN Incorporates oxygen into the indole moiety of tryptophan. Has a broad specificity towards tryptamine and derivatives including D- and L-tryptophan, 5-hydroxytryptophan and serotonin (By similarity).
Publication Abstract from PubMed
Human tryptophan dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) are two important targets in cancer immunotherapy. Extensive research has led to a large number of potent IDO inhibitors; in addition, 52 structures of IDO in complex with inhibitors with a wide array of chemical scaffolds have been documented. In contrast, progress in the development of TDO inhibitors has been limited. Only four structures of TDO in complex with competitive inhibitors that compete with the substrate L-tryptophan for binding to the active site have been reported to date. Here we systematically evaluated the structures of TDO in complex with competitive inhibitors with three types of pharmacophores, imidazo-isoindole, indole-tetrazole, and indole-benzotriazole. The comparative assessment of the protein-inhibitor interactions sheds new light into the structure-based design of enzyme-selective inhibitors.
Structural Insights into Protein-Inhibitor Interactions in Human Tryptophan Dioxygenase.,Geeraerts Z, Ishigami I, Lewis-Ballester A, Pham KN, Kozlova A, Mathieu C, Frederick R, Yeh SR J Med Chem. 2024 Aug 6. doi: 10.1021/acs.jmedchem.4c01360. PMID:39106326[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Geeraerts Z, Ishigami I, Lewis-Ballester A, Pham KN, Kozlova A, Mathieu C, Frédérick R, Yeh SR. Structural Insights into Protein-Inhibitor Interactions in Human Tryptophan Dioxygenase. J Med Chem. 2024 Aug 6. PMID:39106326 doi:10.1021/acs.jmedchem.4c01360
