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Trace derivatives of kynurenine potently activate the aryl hydrocarbon receptor (AHR)
| Content Provider | Scilit |
|---|---|
| Author | Seok, Seung-Hyeon Ma, Zhi-Xiong Feltenberger, John B. Chen, Hongbo Chen, Hui Scarlett, Cameron Lin, Ziqing Satyshur, Kenneth A. Cortopassi, Marissa Jefcoate, Colin R. Ge, Ying Tang, Weiping Bradfield, Christopher A. Xing, Yongna |
| Copyright Year | 2018 |
| Description | Journal: Journal of Biological Chemistry Cellular metabolites act as important signaling cues, but are subject to complex unknown chemistry. Kynurenine is a tryptophan metabolite that plays a crucial role in cancer and the immune system. Despite its atypical, non-ligand-like, highly polar structure, kynurenine activates the aryl hydrocarbon receptor (AHR), a PER, ARNT, SIM (PAS) family transcription factor that responds to diverse environmental and cellular ligands. The activity of kynurenine is increased 100–1000-fold by incubation or long-term storage and relies on the hydrophobic ligand-binding pocket of AHR, with identical structural signatures for AHR induction before and after activation. We purified trace-active derivatives of kynurenine and identified two novel, closely related condensation products, named trace-extended aromatic condensation products (TEACOPs), which are active at low picomolar levels. The synthesized compound for one of the predicted structures matched the purified compound in both chemical structure and AHR pharmacology. Our study provides evidence that kynurenine acts as an AHR pro-ligand, which requires novel chemical conversions to act as a receptor agonist. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808761/pdf http://www.jbc.org/content/293/6/1994.full.pdf |
| Ending Page | 2005 |
| Page Count | 12 |
| Starting Page | 1994 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.ra117.000631 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 6 |
| Volume Number | 293 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2018-02-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Aryl Hydrocarbon Receptor (ahr) (ahr) Ligand-binding Protein Structural Determinants Structure-function |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
