One Key and Multiple Locks: Substrate Binding in Structures of Tryptophan Dioxygenases and Hydroxylases.
Andrea MammoliAlessandra RiccioElisa BianconiAlice ColettiEmidio CamaioniAntonio MacchiaruloPublished in: ChemMedChem (2021)
Since its discovery at the beginning of the past century, the essential nutrient l-Tryptophan (l-Trp) and its catabolic pathways have acquired an increasing interest in an ever wider scientific community for their pivotal roles in underlying many important physiological functions and associated pathological conditions. As a consequence, enzymes catalyzing rate limiting steps along l-Trp catabolic pathways - including IDO1, TDO, TPH1 and TPH2 - have turned to be interesting drug targets for the design and development of novel therapeutic agents for different disorders such as carcinoid syndrome, cancer and autoimmune diseases. This article provides a fresh comparative overview on the most recent advancements that crystallographic studies, biophysical and computational works have brought on structural aspects and molecular recognition patterns of these enzymes toward l-Trp. Finally, a conformational analysis of l-Trp is also discussed as part of the molecular recognition process governing the binding of a substrate to its cognate enzymes.
Keyphrases
- single molecule
- healthcare
- mental health
- small molecule
- dna binding
- high throughput
- binding protein
- molecular dynamics simulations
- emergency department
- molecular dynamics
- squamous cell
- squamous cell carcinoma
- case report
- amino acid
- young adults
- heat shock
- adverse drug
- transcription factor
- oxidative stress
- structural basis
- childhood cancer