Crystal structure of GABA-aminotransferase, a target for antiepileptic drug therapy

gamma-Aminobutyrate aminotransferase (GABA-AT), a pyridoxal phosphate-depen dent enzyme, is responsible for the degradation of the inhibitory neurotran smitter GABA and is a target for antiepileptic drugs because its selective inhibition raises GABA concentrations in brain. The X-ray structure of pig GABA-AT has been determined to 3.0 Angstrom resolution by molecular replace ment with the distantly related enzyme ornithine aminotransferase. Both ome ga-aminotransferases have the same fold, but exhibit side chain replacement s in the closely packed binding site that explain their respective specific ities. The aldimines of GABA and the antiepileptic drug vinyl-GABA have bee n modeled into the active site.