title: Ligand recognition in mu opioid receptor: experimentally based modeling of mu opioid receptor binding sites and their testing by ligand docking.
abstract: For three-dimensional understanding of the mechanisms that control potency and selectivity of the ligand binding at the atomic level, we have analysed opioid receptor-ligand interaction based on the receptor's 3D model. As a first step, we have constructed molecular models for the multiple opioid receptor subtypes using bacteriorhodopsin as a template. The S-activated dihydromorphine derivatives should serve as powerful tools in mapping the three-dimensional structure of the mu opioid receptor, including the nature of the agonist-mediated conformational change that permits G protein-coupling to "second messenger' effector molecules, and in identifying specific ligand-binding contacts with the mu opioid receptor. The analyses of the interactions of some opioid ligands with the predicted ligand binding sites are consistent with the results of the affinity labeling experiments.
authors.affiliation: Institute of Synthetic Organic Chemistry, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sagara
authors.forename: H
authors.initials: H
authors.lastname: Egashira
authors.forename: M
authors.initials: M
authors.lastname: Okamura
authors.forename: I
authors.initials: I
authors.lastname: Fujii
authors.forename: Y
authors.initials: Y
authors.lastname: Shimohigashi
authors.forename: K
authors.initials: K
authors.lastname: Kanematsu
mesh_terms: D000345:Affinity Labels; D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D003198:Computer Simulation; D017124:Conserved Sequence; D003545:Cysteine / Q000378:metabolism; D004090:Dihydromorphine / Q000737:chemistry / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008297:Male; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017450:Receptors, Opioid, mu / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D000345:Affinity Labels; D008024:Ligands; D017450:Receptors, Opioid, mu; D001224:Aspartic Acid; D004090:Dihydromorphine; D003545:Cysteine