Dielectric features of neurotransmitters, γ-aminobutyric acid and L-glutamate, for molecular recognition by receptors

The neurotransmitters gamma-aminiobutyric acid (GABA) and L-glutamate (Glu) have confined plate and disk geometries caused by 2 and 3 tightly hydrated water molecules in aqueous solution, respectively. They also have large dipole moments (mu): ca. 14 and 7.1 D, respectively. The direction of mu for both GABA and Gin is included in planes of the plate and disk geometries. Moreover, mu is parallel to the long molecular axis for GABA, whereas it is perpendicular to the long axis for Glu. Receptors for these neurotransmitters bear a clamshell -like bi-lobate structure in their ligand binding regions and maintain an open-close motion of the two lobes at a rate of similar to10(8) s(-1) in aqueous solution. These receptors detect differences in magnitude and direction of p for GABA and Glu, allowing correct molecular recognition. As the first step of the molecular recognition process, the receptors effectively control the orientation of GABA and Glu via dipole-dipole interaction between their p and a time-dependent dipole moment, i.e., an electric field is generated between the binding sites on the moving lobes.