Fig. 6: NCC inhibition mechanisms of different thiazide diuretics.
From: Molecular mechanisms of thiazide-like diuretics-mediated inhibition of the human Na-Cl cotransporter
a Superposition of the TMDs of CTN-, IDP-, and PTZ-bound NCC structures, which are colored tan, light blue, and white, respectively. The color scheme is the same in (b, c). The bound ligands are shown as color matched sticks. For clarity, the cap domains are not shown. b Structural comparisons of TM3 and TM10 in the inward-facing (yellow) and outward-facing (CTN-, IDP-, or PTZ-bound) NCC. Movements of individual helices during outward-facing to inward-facing conformational switches are indicated with red arrows. c Relationships between NCC’s Cl−-binding site and the chlorine groups of bound chlorthalidone, indapamide, and polythiazide molecules. The Cl−-binding site is outlined with a green dashed circle, and Cl−-coordinating residues are shown as sticks. TM10 is shown as a dashed outline for clarity.
