title: A structure-based approach to understanding somatostatin receptor-4 agonism (sst4).
abstract: It has been reported that somatostatin receptor subtypes 4 and 5 would be high-impact templates for homology modeling if their 3D structures became available. We have generated a homology model of the somatostatin receptor subtype 4 (sst4), using the newest active state β(2) adrenoreceptor crystal structure, and subsequently docked a variety of agonists into the model-built receptor to elucidate the binding modes of reported agonists. Using experimental restraints, we were able to explain observed activity profiles. We propose two binding modes that can consistently explain findings for high-affinity agonists and reason why certain structures display low affinities for the receptor.
authors.affiliation: Department of Chemistry, Southern Illinois University Edwardsville, Edwardsville, Illinois 62026, USA.
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Liu
authors.forename: A Michael
authors.initials: AM
authors.lastname: Crider
authors.forename: Daniel
authors.initials: D
authors.lastname: Ansbro
authors.forename: Christina
authors.initials: C
authors.lastname: Hayes
authors.forename: Maria
authors.initials: M
authors.lastname: Kontoyianni
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011943:Receptors, Adrenergic, beta / Q000737:chemistry*; D017481:Receptors, Somatostatin / Q000819:agonists / Q000737:chemistry*; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D011943:Receptors, Adrenergic, beta; D017481:Receptors, Somatostatin; C098681:somatostatin receptor subtype-4