Figure 6.

Water flux map of A_2A AR. Schematics of the water flux map (apo, agonist-bound, and antagonist-bound forms from the left to the right) are drawn based on the water dynamics from Movie S1, Movie S2, and Movie S3. The major and minor paths of water flux are depicted in solid and dashed lines, respectively. The key microswitches are depicted in sticks, and the residues of the three major structural motifs, i.e., R102^3.50 of DRY, W246^6.48 of CWxP, and Y288^7.53 of NPxxY, are enclosed in the boxes. In the agonist-bound form, the microswitches (N24^1.50, D52^2.50, N280^7.45, N284^7.49, and S281^7.46) in TM1, 2, and 7 form a water cluster and block the water flux. The breakage of the ionic-lock brings R102^3.50 closer to Y288^7.53 in TM7, blocking the entry of water from the IC domain. To see this figure in color, go online.