title: Construction of hypothetical three-dimensional structure of P2Y1 receptor based on Fourier transform analysis.
abstract: G protein-coupled receptors constitute a large family of homologous transmembrane proteins that represents one of the most important classes of confirmed drug targets. For novel drug discovery, the 3D structure of target protein is indispensable. To construct hypothetical 3D structures of G protein-coupled receptors, several prediction methods have been proposed. But none of the them has confirmed a correct ligand binding site. In this study we constructed the 3D structure of bovine rhodopsin using the prediction method proposed by Donnelly et al., with some modification. We found that our 3D model showed a good agreement with the reported retinal binding site. Using the similar method, we constructed the 3D structure of the P2Y1 receptor; one of the G protein-coupled receptors, and showed a binding site of an endogenous ligand, ADP, on the basis of the 3D model and in vitro experimental data. These results should be valuable for design of a specific antagonist for P2Y1 receptor.
authors.affiliation: Laboratory of Bio-signaling chemistry Department of Bioscience and Biotechnology, Ritsumeikan University 1-1-1 Noji-higashi, Kusatsu 525-8577, Japan. rb051958@se.ritsumei.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hiramoto
authors.forename: Wataru
authors.initials: W
authors.lastname: Nemoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Norihisa
authors.initials: N
authors.lastname: Fujita
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D000465:Algorithms; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry; D008958:Models, Molecular; D015233:Models, Statistical; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D018048:Receptors, Purinergic P2 / Q000737:chemistry*; D058472:Receptors, Purinergic P2Y1; D012243:Rhodopsin / Q000737:chemistry; D012984:Software; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*
chemical_list: D008024:Ligands; D008565:Membrane Proteins; C546382:P2RY1 protein, human; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D000244:Adenosine Diphosphate; D012243:Rhodopsin; D019204:GTP-Binding Proteins