Fig. 5: Comparison of TAS2R14 with TAS2R46.
From: A bitter anti-inflammatory drug binds at two distinct sites of a human bitter taste GPCR
a, b A view of FFA (orange, a) and strychnine (Str, cyan, PDB 7XP6, b) at the TAS2R binding pocket. TAS2R14 is in green (a), and TAS2R46 in gray (b) Gustducin is shown in gold for both receptors. c Superposition of FFA and Str within the canonical binding pocket reveals different binding modes for the two ligands. FFA extends into a cavity localized towards the extracellular milieu. The cavity is highlighted in green and composes the hydrophobic pocket that accommodates the trifluoromethyl moiety. Str clashes with the inward TM7 position of TAS2R14, thus there is an outward movement of TM7 at the extracellular site. The clash is presented in red. Residue and helix numbers are indicated in the figure. TAS2R14 is green, TAS2R46 is grey. d, e Comparison of TM arrangement in the canonical binding pocket reveals major changes in the orientation of TMs 2,4,5 and 7 in the bound structures of TAS2R14 (green) and TAS2R46 (gray). A side view is in (d), top view is presented in (e). f Superposition of TAS2R14 (green) and TAS2R46 (gray) reveals that in the intracellular face, TM arrangement is identical for both receptors, apart from an outward movement of TM6 in TAS2R14. A clash with TM6 position in TAS2R46 (that lacks the second pocket) is indicated in red.
