Computational analysis of the structural basis of ligand binding to the crustacean retinoid X receptor.

Homodimerization of the retinoid X receptor (RXR) occurs upon binding of ligands to the receptor, but little is known about structural mechanisms involved in RXR ligand binding. In the present study, binding of known ligands (5-Hydroxytryptamine, dopamine and naloxone) to the Celuca pugilator RXR was modeled computationally using the human RXR-α as a homology template. Docking scores calculated for these ligands showed reasonably good binding interactions to C. pugilator RXR. Furthermore, RXR is the receptor that mediates the different activities of neurotransmitters and opioid against naloxone in crustaceans and possibly other species. These results indicate that 5-hydroxytryptamine and naloxone might have similar functions. These also results suggest a 3-D model of C. pugilator RXR that describes the binding of ligands at a single RXR receptor binding site and offers further insight into the binding of structurally diverse ligands to this receptor. Further, computational studies showed that crustacean RXRs might be closer to vertebrate RXR than to insect RXR. The predicted binding models for C. pugilator RXR may allow for better design of experimental studies, such as site-directed mutagenesis and affinity labeling studies that may yield valuable information concerning structure-activity relationship studies of RXR and its ligands.