Computer model of the active conformation of the NR2E3 LBD reveals a putative open ligand-binding pocket.

Abstract

<p><b>A</b>. Overlay of the apo LBDs of NR2E3 (purple) and RXR (green). <b>B</b>. Overlay of the LBDs of apo NR2E3 (purple) and agonist-bound RXR (lime green). The main difference between the ligand binding pockets lies in the extension of helix 10 in agonist-bound RXR. <b>C</b>. Computer model (SWISS Model) of the NR2E3 LBD in an active conformation based on the agonist-bound RXRα structure, with helix 10 extended. A ligand binding pocket of 578 ų was found in this conformation. The pocket volume and the surface (grey mash) were calculated using the program VOIDOO. <b>D</b>. Close-up of the potential ligand binding pocket in the active model of the NR2E3 LBD and its surrounding residues. <b>E</b>. 9-<i>cis</i> retinoic acid (ball model), which has limited NR2E3 agonistic properties [37], fits well into the modeled ligand binding pocket.</p