title: Molecular evolution of adrenoceptors and dopamine receptors: implications for the binding of catecholamines.
abstract: We derived homology models for all human catecholamine-binding GPCRs (CABRs; the alpha-1, alpha-2, and beta-adrenoceptors and the D1-type and D2-type dopamine receptor) using the bovine rhodopsin-11-cis-retinal X-ray structure. Interactions were predicted from the endogenous ligands norepinephrine or dopamine and from the binding site and were used to optimize receptor-ligand interactions. Similar binding modes in the complexes agree with a large "binding core" conserved across the CABRs, that is, D3.32, V(I)3.33, T3.37, S5.42, S(A/C)5.43, S5.46, F6.51, F6.52, and W6.48. Model structures and docking simulations suggest that extracellular loop 2 could provide a common attachment point for the ligands' beta-hydroxyl via a hydrogen bond donated by the main-chain NH group of residue xl2.52. The modeled CABRs and docking modes are in good agreement with published experimental studies. Complementarity between the ligand and the binding site suggests that the bovine rhodopsin structure is a suitable template for modeling agonist-bound CABRs.
authors.affiliation: Department of Biochemistry and Pharmacy, Abo Akademi University, FI-20520 Turku, Finland.
authors.forename: Henri
authors.initials: H
authors.lastname: Xhaard
authors.forename: Ville-Veikko
authors.initials: VV
authors.lastname: Rantanen
authors.forename: Tommi
authors.initials: T
authors.lastname: Nyrönen
authors.forename: Mark S
authors.initials: MS
authors.lastname: Johnson
mesh_terms: D000322:Adrenergic Agonists / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002395:Catecholamines / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D018491:Dopamine Agonists / Q000737:chemistry; D019143:Evolution, Molecular; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D011941:Receptors, Adrenergic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012172:Retinaldehyde / Q000737:chemistry; D012243:Rhodopsin / Q000737:chemistry
chemical_list: D000322:Adrenergic Agonists; D002395:Catecholamines; D018491:Dopamine Agonists; D008024:Ligands; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D012243:Rhodopsin; D012172:Retinaldehyde