Bitter taste is one of the basic taste modalities, needed to guard the animal against consuming toxic substances which are often bitter. Bitter compounds are recognized by bitter taste receptors (TAS2Rs), a family of broadly tuned G-protein coupled receptors (GPCRs).How do these receptors detect numerous structurally diverse bitter compounds?Do different receptors with overlapping specificities recognize their ligands in the same way?
Molecular modeling and computational docking of a bitter ligand into different receptors which it activates1-3, as well as docking of various ligands into a single associated receptor3, are used to elucidate the molecular details of recognition and receptors receptive range. In parallel, BitterDB http://bitterdb.agri.huji.ac.il/bitterdb/, the resource of bitter compounds which we recently established4, is analyzed to characterize the structures and chemical properties of known bitter ligands. Combining these findings with state-of-the-artin-silicoapproaches, we identify previously unknown bitter ligands as well as novel associations between compounds and bitter taste receptors.
Our results shed light on the molecular details of bitter taste recognition and provide new directions in the identification and design of agonists and antagonists for bitter taste receptors.
Dr. Masha Niv masha.niv@mail.huji.ac.il
References:
1. Levit, A., Barak, D., Behrens, M., Meyerhof, W. & Niv, M.Y. Homology model-assisted elucidation of binding sites in GPCRs. Methods Mol Biol 914, 179-205 (2012).
2. Brockhoff, A., Behrens, M., Niv, M.Y. & Meyerhof, W. Structural requirements of bitter taste receptor activation. Proc Natl Acad Sci U S A 107, 11110-5 (2010).
3. Born, S., Levit, A., Niv, M.Y., Meyerhof, W. & Behrens, M. The Human Bitter Taste Receptor TAS2R10 Is Tailored to Accommodate Numerous Diverse Ligands. J Neurosci 33, 201-13 (2013).
4. Wiener, A., Shudler, M., Levit, A. & Niv, M.Y. BitterDB: a database of bitter compounds. Nucleic Acids Res 40, D413-9 (2012).
