BitterDB: a database of bitter compounds

Abstract

Basic taste qualities like sour, salty, sweet, bitter and umami serve specific functions in identifying food components found in the diet of humans and animals, and are recognized by proteins in the oral cavity. Recognition of bitter taste and aversion to it are thought to protect the organism against the ingestion of poisonous food compounds, which are often bitter. Interestingly, bitter taste receptors are expressed not only in the mouth but also in extraoral tissues, such as the gastrointestinal tract, indicating that they may play a role in digestive and metabolic processes. BitterDB database, available at http://bitterdb.agri.huji.ac.il/bitterdb/, includes over 550 compounds that were reported to taste bitter to humans. The compounds can be searched by name, chemical structure, similarity to other bitter compounds, association with a particular human bitter taste receptor, and so on. The database also contains information on mutations in bitter taste receptors that were shown to influence receptor activation by bitter compounds. The aim of BitterDB is to facilitate studying the chemical features associated with bitterness. These studies may contribute to predicting bitterness of unknown compounds, predicting ligands for bitter receptors from different species and rational design of bitterness modulators.

Figure 1.

Screenshots of the BitterDB interface. (A) Illustration of three available search options: (i) Simple search: search compounds using keywords. (ii) Structure-based similarity search: 2D similarity search using different structural formats (drawing, smiles and user uploaded structure files). (iii) Advanced search, including searching by chemical descriptors, molecule identifiers and by associated human bitter taste receptors. Orphan receptors (shown in gray) cannot be searched by ligands. (B) The BitterDB compound browse table (which can be sorted by different criteria). (C) An example of a query result page: the user can download an SDF file of selected compounds from the result page. (D) A representative compound entry page.

Figure 2.

2D transmembrane protein diagram. A convenient representation of the receptor sequence and its TM regions, shown here for hTAS2R16. The seven TM helices are displayed as predicted by Topcons. The most conserved residue in each helix X (BW number X.50) has black background. Residues for which mutation data are available are marked with red, and information about the mutations can be found in the site ‘Known Mutations Table’ section below the diagram http://bitterdb.agri.huji.ac.il/bitterdb/Receptor.php?id=16#ReceptorKnownMutations.

Figure 3.

A subset of four hTAS214 ligands demonstrating a high degree of structural variability. These four structurally diverse compounds, which are all hTAS214 ligands, demonstrate that hTAS214 ligands lie in a broad chemical spectrum that includes compounds from different classes such as aromatic polycyclic compounds (1), polyacetylenes (2), sulfoxides (3) and cycloparaffins (4).