Structural model of antagonist and agonist binding to the angiotensin II, AT1 subtype, G protein coupled receptor

摘要: Abstract Background: The family of G protein coupled receptors is the largest and perhaps most functionally diverse class cell-surface receptors. Due to difficulty obtaining structural data on membrane proteins there little information which base an understanding ligand structure-activity relationships, effects receptor mutations mechanism(s) signal transduction in this family. We therefore set out develop a model for one such receptor, human angiotensin II receptor. Results: An alignment between (type 1; hATI), β2 adrenergic, neurokinin-1, bradykinin receptors, all are was used generate three-dimensional hATI based bacteriorhodopsin. observed region within that congruent with biogenic amine binding site β2, were thus able dock hAT 1 antagonist L-158,282 (MK-996) into transmembrane model. oriented helical domain by recognising essential acid functionality interacts Lys199. consistent much relationships both non-peptide peptide ligands. Conclusions: Our provides explanation conversion agonist addition isobutyl group. It also suggests motion during transduction. approach independently deriving models pharmacophore ligands, then combining them, powerful technique helps validate models.