title: Homology models of melatonin receptors: challenges and recent advances.
abstract: Melatonin exerts many of its actions through the activation of two G protein-coupled receptors (GPCRs), named MT1 and MT2. So far, a number of different MT1 and MT2 receptor homology models, built either from the prototypic structure of rhodopsin or from recently solved X-ray structures of druggable GPCRs, have been proposed. These receptor models differ in the binding modes hypothesized for melatonin and melatonergic ligands, with distinct patterns of ligand-receptor interactions and putative bioactive conformations of ligands. The receptor models will be described, and they will be discussed in light of the available information from mutagenesis experiments and ligand-based pharmacophore models. The ability of these ligand-receptor complexes to rationalize structure-activity relationships of known series of melatonergic compounds will be commented upon.
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy. silvia.rivara@unipr.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Pala
authors.forename: Alessio
authors.initials: A
authors.lastname: Lodola
authors.forename: Annalida
authors.initials: A
authors.lastname: Bedini
authors.forename: Gilberto
authors.initials: G
authors.lastname: Spadoni
authors.forename: Silvia
authors.initials: S
authors.lastname: Rivara
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D006801:Humans; D008024:Ligands; D008550:Melatonin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D044122:Receptor, Melatonin, MT1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D008550:Melatonin