NMR structure of the thromboxane A2 receptor ligand recognition pocket.

摘要: To overcome the difficulty of characterizing structures extracellular loops (eLPs) G protein-coupled receptors (GPCRs) other than rhodopsin, we have explored a strategy to generate three-dimensional structural model for GPCR, thromboxane A2 receptor. This structure was completed by assembly NMR computation-guided constrained peptides that mimicked and connected conserved seven transmembrane domains. The structure-based reveals features eLPs, in which second loop (eLP2) disulfide bond between first (eLP1) eLP2 play major role forming ligand recognition pocket. conformation is dynamic regulated oxidation reduction bond, affects docking initial recognition. reduced form receptor experienced decrease binding activity due rearrangement conformation. ligand-bound was, however, resistant inactivation because covered stabilized molecular mechanism may be applied prostanoid GPCRs.