Figure 7.

Human TRPV4 ligand binding site. a, schematic representation of the apo structure of TRPV4 channel (white ribbon) with the identified ligand binding site highlighted in light purple. b, zoomed-in view of the ligand binding pocket shown in a, (purple ribbon). c, zoomed-in view of the structure of TRPV4 in the open-state in complex with agonists 4α-PDD (orange ribbon) and d, GSK1016790A (pink ribbon). Closed-state structures in complex with antagonists are shown in e, HC-067047 (blue ribbon) and f, GSK2798745 (cyan ribbon). The side chains of the polar and aromatic residues essential for binding agonists and antagonists (shown in gray) are represented as sticks. Hydrogen bonds are represented as dashed lines. Both agonists and antagonists are stably positioned within the ligand binding pocket and share some residues with which they interact, such as S470, N474, F524, N528, Y553, Y591, D743, and S747. However, they are also closely surrounded by particular residues: 4α-PDD (F478); GSK1016790A (Q550, D531, F549, L523); HC-067047 (Y478, F592) and GSK2798745 (Y478, F524). PDB: 8T1B, 8FCA, 8FC7, and 8FC8 (resolutions of 3.00 Å, 3.41 Å, 3.30 Å and 3.47 Å, respectively) [52,53]. Created with PyMOL and BioRender.com.