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.