Identification of the second extracellular loop in G-protein coupled neurotransmitter receptors as the site for ligand recognition, using spectral map analysis

From the comparison of the primary structures of G-protein coupled receptors a graphical receptor classification is obtained with the use of spectral map analysis. The resulting “receptor map” represents the relationships among receptors in a space of reduced dimensionality. It is found that the receptors can be classified according to the comparison of the complete amino acid sequences, the transmembrane part of the sequences, the third transmembrane part of the sequences or the part of the sequences defining the second extracellular loop (0–2) connecting the fourth and fifth transmembrane domains. These results suggest that this loop acts as a recognition site for ligands and inspired the molecular modelling for the CYANETCC 191 part of the 0–2 loop in the human β 2 -receptor. The molecular modelling and computation indeed support the recognition and molecular interaction between the residue side chains of Tyr 185 and Glu 188 and a molecular probe representing β 2 -receptor ligands.