InterPro domain: IPR010107

This entry represents glutamate decarboxylase (Gad; 4.1.1.15 ) it is a pyridoxal 5'-phosphate (PLP)-dependent enzyme, which catalyses the irreversible alpha-decarboxylation of L-glutamate to gamma-aminobutyrate (GABA). This enzyme is widely distributed amongst eukaryotes and prokaryotes, but its function varies in different organisms [ 1 ].

GadD has a crucial role in the vertebrate central nervous system where it is responsible for the synthesis of GABA, the major inhibitory neurotransmitter. In the majority of vertebrates Gad occurs in two isoforms, Gad65 and Gad67, both active at neutral pH [ 2 ]. Gad isoforms (GadA and GadB) have also been reported in some bacterial species, including the Gram-negative bacterium [ 3 ] and Gram-positive bacterium [ 4 ].

A unique feature of plant and yeast Gad is the presence of a calmodulin (CaM)-binding domain in the C-terminal region. In Saccharomyces cerevisiae (Baker's yeast), Gad expression is required for normal oxidative stress tolerance [ 5 ]. In plants, Gad is thought to be a stress-adapter chaperonin sensing Ca2+ signals.

1. Crystal structure and functional analysis of Escherichia coli glutamate decarboxylase. EMBO J. 22, 4027-37
2. Two isoforms of glutamate decarboxylase: why? Trends Pharmacol. Sci. 19, 500-5
3. Escherichia coli has two homologous glutamate decarboxylase genes that map to distinct loci. J. Bacteriol. 174, 5820-6
4. A glutamate decarboxylase system protects Listeria monocytogenes in gastric fluid. Mol. Microbiol. 40, 465-75
5. Expression of a glutamate decarboxylase homologue is required for normal oxidative stress tolerance in Saccharomyces cerevisiae. J. Biol. Chem. 276, 244-50