Differentiating enantioselective actions of GABOB: a possible role for threonine 244 in the binding site of GABA(C) ρ(1) receptors.

ABSTRACT: Designing potent and subtype-selective ligands with therapeutic value requires knowledge about how endogenous ligands interact with their binding site. 4-Amino-3-hydroxybutanoic acid (GABOB) is an endogenous ligand found in the central nervous system in mammals. It is a metabolic product of GABA, the major inhibitory neurotransmitter. Homology modeling of the GABA(C) ρ(1) receptor revealed a potential H-bond interaction between the hydroxyl group of GABOB and threonine 244 (T244) located on loop C of the ligand binding site of the ρ(1) subunit. Using site-directed mutagenesis, we examined the effect of mutating T244 on the efficacy and pharmacology of GABOB and various ligands. It was found that mutating T244 to amino acids that lacked a hydroxyl group in their side chains produced GABA in

SUBMITTER: Yamamoto I 

PROVIDER: S-EPMC3447397 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature