title: Homology modelling and binding site mapping of the human histamine H1 receptor.
abstract: Three-dimensional model of the human histamine H1 receptor was developed by homology modelling using the high resolution structure of bovine rhodopsin as template. Genetic algorithm based docking calculations were used to identify the role of several amino acids having an effect on agonist or antagonist binding. Binding mode analyses of mepyramine, desloratidine, loratidine and acrivastine allowed us to rationalise their binding affinity. Binding site mapping resulted in seven new potential aromatic interaction points (Tyr 108, Phe 184, Phe 190, Phe 199, Phe 424, Trp 428, Tyr 431), that took part in forming the lipophilic pocket of the antagonist binding cavity.
authors.affiliation: Department of Computer Assisted Drug Discovery, Gedeon Richter Ltd., H-1475, Budapest 10, P.O. Box 27, Hungary.
authors.forename: Róbert
authors.initials: R
authors.lastname: Kiss
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kovári
authors.forename: György M
authors.initials: GM
authors.lastname: Keseru
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002417:Cattle; D003198:Computer Simulation; D004347:Drug Interactions; D017442:Histamine Agonists / Q000737:chemistry* / Q000378:metabolism; D006633:Histamine Antagonists / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D017336:Loratadine / Q000031:analogs & derivatives* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D011738:Pyrilamine / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014311:Triprolidine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D017442:Histamine Agonists; D006633:Histamine Antagonists; D011969:Receptors, Histamine H1; D014311:Triprolidine; D017336:Loratadine; D012243:Rhodopsin; C043648:acrivastine; C121345:desloratadine; D011738:Pyrilamine