Substrate stereospecificity and active site topography of gamma-aminobutyric acid aminotransferase for beta-aryl-gamma-aminobutyric acid analogues.

The substrate and inhibitory properties of (R)- and (S)-4-amino-3-phenylbutanoic acid, (R)- and (S)-4-amino-3-(4-chlorophenyl)butanoic acid (baclofens), (E)-4-amino-3-phenylbut-2-enoic acid, and (E)-4-amino-3-(4-chlorophenyl)but-2-enoic acid are determined and compared with those of 4-aminobutanoic acid, 4-aminobut-2-enoic acid (4-aminocrotonic acid), and the racemic mixtures of 4-amino-3-arylbutanoic acids. All compounds in both series were found to be substrates, except for the R-isomers, which were identified as competitive inhibitors. These results are compared with known pharmacological data regarding the appropriate isomers.