Ligand Binding and Functional Selectivity of l-Tryptophan Metabolites at the Mouse Aryl Hydrocarbon Receptor (mAhR)
The aryl hydrocarbon receptor (AhR) is a nuclear receptor regulating a wide range of biological and toxicological effects. Metabolites of l-tryptophan are able to bind and activate AhR, providing a link between tryptophan catabolism and a novel mechanism of protective tolerance, referred to as “disease tolerance”. The notion that pharmacologic modulation of genes associated with endotoxin tolerance would be beneficial in clinical settings dominated by acute hyperinflammatory responses to infection thrusts AhR into the limelight as an interesting druggable target. Combining homology modeling, docking studies, and molecular dynamic simulations with mutagenesis experiments and gene profiling, in this work we report that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and two different l-tryptophan metabolites, namely l-Kynurenine and FICZ (6-formylindolo[3,2-b]carbazole), are able to bind to mAhR, exploiting different key interactions with distinct set of fingerprint residues. As a result, they stabilize differen...
Roberto Nuti; Marco Gargaro; Davide Matino; Daniela Dolciami; Ursula Grohmann; Paolo Puccetti; Francesca Fallarino; Antonio Macchiarulo
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Resonantly driven quantum emitters offer a very promising route to obtain highly coherent sources of single photons required for applications in quantum information processing (QIP). Realizing this for on-chip scalable devices would be important for scientific advances and practical applica ... more
Rohm and Haas Powder Coatings is delighted to announce that its Reading, Pennsylvania, facility is the first site in the world to receive the RCMS® Site Certification awarded by the American Chemical Council (ACC).
When Raj Gupta, Chairman and CEO of Rohm and Haas Company, became Chairman ... more