The orphan G-protein coupled recept

The orphan G-protein coupled receptor GPR55 was shown to bind to certain cannabinoid compounds
which led to its initial classification as the third type of cannabinoid receptor. Later studies showed
that lysophosphatidylinositol (LPI) also activated GPR55, in particular 2-arachidonoyl-LPI was proposed
to be its endogenous ligand. However, the results of pharmacological studies regarding GPR55 have
been quite inconsistent. Despite its contradictory pharmacological profile, GPR55 has been implicated
in various disease states including inflammatory and neuropathic pain, metabolic bone diseases, and
cancer. Herein, we report the ligand binding properties of GPR55 by applying homology modeling and
automated docking algorithms in order to understand its pharmacological profile. The 3D homology
model of GPR55 was built based on the adenosine A2A receptor crystal structure. Docking studies of
several types of reported ligands were carried out afterwards. The results indicated that both hydrogen
bonding and hydrophobic interactions contributed significantly for its ligand binding and the amino acid
residue Lys80 seemed to be the anchor residue for receptor recognition. In addition, its putative agonist
and antagonist appeared to recognize different domains of the receptor corresponding to their reported
pharmacological activities