TAS2R13

TAS2R13 is a functional bitter taste receptor that responds to structurally diverse agonists and is subject to inhibition by plant-derived phenolics. It is activated by the anti-HIV protease inhibitors lopinavir and ritonavir, as shown by calcium mobilization in receptor-expressing cells (PMID:37625013). Its activity is inhibited by Morus alba leaf extract (PMID:37796414) and by phenolic acids and flavonoids from Cornelian cherry, including naringin and quercetin, with these compounds engaging the receptor in a manner comparable to model agonists (PMID:38987427). Ligand recognition occurs at a half-open cavity at the receptor's N-terminal region, mediated by hydrogen-bond and hydrophobic interactions (PMID:37229471). Beyond ligand activation and inhibition characterized through cell-based calcium assays and docking, no downstream signaling partners or structural model have been characterized in the available corpus.

1. 2023 Medium

   Establishing that TAS2R13 is a functional receptor with identifiable agonists answered whether specific drug molecules can trigger its activity, linking bitter perception to off-target taste responses of clinical compounds.

   Evidence Calcium mobilization assay in cells expressing TAS2R13, tested with lopinavir and ritonavir

   PMID:37625013

   Open questions at the time

   • Single lab, single functional method
   • Downstream G-protein coupling and signaling cascade not defined
   • No dose-response potency comparison across receptors reported here
2. 2023 Low

   Computational docking addressed where ligands bind on TAS2R13, locating a half-open N-terminal cavity engaged through hydrogen-bond and hydrophobic contacts.

   Evidence Molecular docking / in silico binding affinity analysis of theasinensin A against TAS2R13

   PMID:37229471

   Open questions at the time

   • Computational docking only, no experimental functional validation of theasinensin A binding to TAS2R13
   • No experimental structure of the receptor
   • Predicted cavity not confirmed by mutagenesis
3. 2023 Medium

   Identifying that a plant extract suppresses TAS2R13 activity established the receptor as a target for bitterness inhibition, not only activation.

   Evidence Calcium release assay in transfected HEK293T cells with Morus alba leaf extract

   PMID:37796414

   Open questions at the time

   • Active inhibitory constituents within the extract not isolated
   • Mechanism of inhibition (orthosteric vs allosteric) undefined
   • Single lab, single method
4. 2024 Medium

   Pairing docking with functional assays identified specific flavonoids that inhibit TAS2R13 and compared their binding behavior to model agonists, refining structure-activity understanding of the receptor.

   Evidence Molecular docking combined with calcium-based inhibition functional assay in receptor-expressing cells, testing Cornelian cherry phenolics including naringin and quercetin

   PMID:38987427

   Open questions at the time

   • Single lab
   • Binding poses not validated by mutagenesis or structural data
   • Physiological relevance of inhibition in vivo not tested

• The downstream signaling mechanism, receptor structure, and physiological role of TAS2R13 beyond ligand activation/inhibition remain undefined.
• No experimental structure or validated binding-site residues
• G-protein coupling and intracellular cascade not characterized in the corpus
• In vivo taste or extra-oral physiological role not established