Dielectric Features of Neurotransmitters, γ-Aminobutyric Acid and l-Glutamate, for Molecular Recognition by Receptors

The neurotransmitters γ-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 (μ): ca. 14 and 7.1 D, respectively. The direction of μ for both GABA and Glu is included in planes of the plate and disk geometries. Moreover, μ 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 ∼108 s-1 in aqueous solution. These receptors detect differences in magnitude and direction of μ 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 μ and a time-dependent dipole moment, i.e., an electric field is generated between the binding sites on the moving lobes.