Glutamic acid decarboxylase cDNA: nucleotide sequence encoding an enzymatically active fusion protein.

Glutamic acid decarboxylase (GAD;E.C. 4.1.1.15) catalyzes the production of GABA, the major inhibitory neurotransmitter in the mammalian brain. We recently isolated a lambda gt-11 recombinant, lambda-GAD, that contains the cDNA for GAD from feline brain (Kaufman et al., 1986). Interestingly, the beta-galactosidase-GAD fusion protein encoded by lambda GAD is enzymatically active, catalyzing the conversion of glutamate to CO2 and GABA. Here we report the nucleotide sequence of feline GAD cDNA. It consists of 2265 bases, with a continuous open reading frame of 625 codons. The derived sequence contains the sequence Asn-Pro-His-Lys, which is identical to sequence at the pyridoxal phosphate-binding site of porcine DOPA decarboxylase (Bossa et al., 1977). The first ATG sequence in the open reading frame begins at nucleotide residue 118. The 585 codons 3' to this putative initiation site predict an amino acid composition, N-terminal residue, and molecular size consistent with published characterizations of GAD.