FIGURE 9.

A model of phloretin binding to HsNHA2. Phloretin, shown in yellow, was docked to the crystal structure of human NHA2 (PDB entry 7B4L) as described in Material and Methods and is shown in two different views. Residues within a radius of 5 Å from phloretin are shown as sticks. Phloretin is stabilized by three amino acids. The 2,4,6‐trihydroxyphenyl ring interacts via hydrogen bonds with the side chain hydroxyl of S178 and the backbone carbonyl of R177. It also forms cation‐pi interaction with the side chain guanidinium of R177. The 4‐hydroxyphenyl ring hydrogen bonds with the highly conserved D279 in HsNHA2 binding site, that facilitates both proton and cation transport