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International audience; Odorant-binding proteins (OBPs) are abundant soluble proteins secreted in the nasal mucus of a variety of species which are believed to be involved in the transport of odorants towards olfactory receptors. In this study, we report the functional characterization of mouse OBP5 (mOBP5). mOBP5 was recombinantly expressed as a hexahistidine-tagged protein in bacteria and purified by metal affinity. Oligomeric state and secondary structure composition of mOBP5 was investigated using gel filtration and circular dichroism spectroscopy. Fluorescent experiments revealed that mOBP5 interacts with the fluorescent probe N-phenyl naphthylamine (NPN) with a micromolar affinity. Competitive binding experiments with 40 odorants indicated that mOBP5 binds a restricted number of odorants with a good affinity. Isothermal titration calorimetry (ITC) confirmed that mOBP5 binds these compounds with association constants in the micromolar range. Finally, protein homology modelling and molecular docking analysis revealed the amino acid residues of mOBP5 guiding its binding properties.

Understanding how chemicals code for a certain type of taste is fundamental for the development of a rational method to create new taste modulators. The identification of these new candidates is important for the food industry and would also be beneficial for the pharmacology industry. In humans, the bitter taste depends on a large family of 25 taste receptors type 2 (TAS2Rs) belonging to the G protein-coupled receptor (GPCR) family. They are classified distantly related to class A GPCR and, to date, the experimental structures have not been determined for any TAS2Rs. Here we present a new structure-based virtual screening strategy to expand the chemical space of bitter taste receptors. Combining molecular modeling (based on a recent general approach for modeling all mammal TAS2Rs1) and in vitro functional assays, we identified new active compounds as activators of human TAS2R14. Such agonists will be of broad interest beyond food science since TAS2Rs are ectopically expressed in other parts of the human body besides the tongue.