The crystal structure of PNR's ligand-binding domain is known. It self-dimerizes into, by default, a repressor state. Computer simulations based on this model shows that a ligand could possibly fit into PNR and switch it into a transcription activator.
13-cis retinoic acid is a known weak agonist that fits into such a pocket, but no physiologic ligand is known. Two synthetic compounds, 11A and 11B, appear to be agonists but do not go into the pocket and instead work as
allosteric modulators. A more recent screening identifies another compound called photoregulin-1 (PR1) that functions as a reverse agonist, an activity possibly useful in the management of retinitis pigmentosa. == Clinical significance ==