title: Model of the whole rat AT1 receptor and the ligand-binding site.
abstract: We present a three-dimensional model of the rat type 1 receptor (AT1) for the hormone angiotensin II (Ang II). Ang II and the AT1 receptor play a critical role in the cell-signaling process responsible for the actions of renin-angiotensin system in the regulation of blood pressure, water-electrolyte homeostasis and cell growth. Development of improved therapeutics would be significantly enhanced with the availability of a 3D-structure model for the AT1 receptor and of the binding site for agonists and antagonists. This model was constructed using a combination of computation and homology-modeling techniques starting with the experimentally determined three-dimensional structure of bovine rhodopsin (PDB#1F88) as a template. All 359 residues and two disulfide bonds in the rat AT1 receptor have been accounted for in this model. Ramachandran-map analysis and a 1 nanosecond molecular dynamics simulation of the solvated receptor with and without the bound ligand, Ang II, lend credence to the validity of the model. Docking calculations were performed with the agonist, Ang II and the antihypertensive antagonist, losartan. [Figure: see text].
authors.affiliation: Department of Molecular Cardiology at Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Camelia
authors.initials: C
authors.lastname: Baleanu-Gogonea
authors.forename: Sadashiva
authors.initials: S
authors.lastname: Karnik
mesh_terms: D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D011945:Receptors, Angiotensin / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
chemical_list: D008024:Ligands; D011945:Receptors, Angiotensin; D000804:Angiotensin II