Ashok E. Philip, Jacques H. Poupaert and Christopher R. McCurdy Pages 325 - 340 ( 16 )
The opioid receptor-like 1 (ORL1) system has attracted a lot of attention owing to its diverse physiological role and by its close structural proximity toward the classical opioid receptors. Even though they share a close sequence similarity, the ligand recognition pattern for the ORL1 receptor and the classical opioid receptors remains highly distinct. In addition, functional diversification observed between the ORL1 receptor system and classical opioid receptors clearly indicates that subtle changes in the structural makeup of a receptor are enough to delineate them. A clear understanding of the structural requirements for ligand selectivity by classical opioid receptors and identification of a common “opioid binding pocket” has not been achieved yet. At this juncture, the ORL1 receptor system presents itself as a potential tool in the quest for elucidating critical elements directing ligand selectivity. The current paper is a compilation of several sitedirected mutagenesis studies conducted on the ORL1 receptor system. The mutagenesis studies concentrated on the transmembrane domain residues are reported with the changes observed in terms of both binding and functional activation of the receptor. Given the critical role played by this G-protein coupled receptor, molecular level understanding of this ORL1 receptor system would aid in rational design and development of agonists and antagonists with multiple therapeutic applications.
g-protein coupled receptors(gpcrs), cdna library, opioid receptor agonist, trans-membrane domain, mutagenesis, nociceptin, ethylketocyclazocine, ligands, phenylalanine residues
Department of Medicinal Chemistry, School of Pharmacy, Faser 419, The University of Mississippi,University, MS 38677, USA.