Figure 5.

Tamoxifen binding in the estrogen receptor and the NavMs channel and its inhibition of sodium currents recorded from adenocarcinoma cells

(A) Stereo image of overlays of the 4-hydroxytamoxifen binding sites in NavMs (PDB: 6SXC) (dark green) and in the estrogen receptor (dark pink) (PDB: 3ERT). This shows the similarities of the binding site geometries and residues that form hydrogen bonds (Asp at one end and Glu at other end) involved in the interactions of the compound (shown in corresponding light green and light pink stick depictions) with both target proteins. The side chains of the NavMs and estrogen receptor protein molecules are depicted in dark green and dark pink, respectively.

(B) Endogenous sodium currents recorded from the adenocarcinoma cell line MDA-MB-231 cells. Left: exemplar voltage-gated sodium currents activated by successively increasing the depolarizing potential by 5 mV from a −100 mV holding potential before and after TTX treatment. Right: resulting current densities plotted as a function of voltage.

(C) Left: exemplar I_Na recorded from MDA-MB-231 cells and their inhibition by 4-hydroxytamoxifen using the same protocol described in Figure 4. Right, drug concentration-percentage sodium current inhibition relationships for TTX and 4-hydroxytamoxifen as described in Figure 4. Error bars denote SD, and number of cells tested is indicated in parentheses.

See also Figure S2.