Fig. 5: Molecular basis of hOCT1 inhibition by spironolactone.
From: Structural insights into human organic cation transporter 1 transport and inhibition
a The chemical structure of spironolactone. b, c Spironolactone binds to the central pocket of hOCT1 at the outward facing (hOCT1-S1) (b) and inward facing (hOCT1-S2) (c) conformations. The binding pocket is hydrophobic, as shown by the molecular lipophilicity potential function in Chimera X. d, e Hydrophobic interactions between spironolactone and hOCT1 in the outward facing (hOCT1-S1) (d) and inward facing (hOCT1-S2) (e) conformations. f, g Hydrophilic interactions between spironolactone and hOCT1 in the outward facing (hOCT1-S1) (f) and inward facing (hOCT1-S2) (g) conformations. h Structural comparison of the spironolactone-binding pockets in outward facing (hOCT1-S1) (orange) and inward (hOCT1-S2) (cyan) facing conformations. i–k Inhibition of ASP+ uptake by spironolactone (cyan), progesterone (orange), and estradiol (green) in HEK293T cells stable expressing hOCT1 (i), hOCT2 (j), and hOCT3 (k). Data are shown as mean ± SEM of three independent experiments.
