4-aminobutyrate aminotransferase (Escherichia coli) (GabT)

4-aminobutyrate aminotransferase (GabT) is a pyridoxal phosphate (PLP)-dependent enzyme in Escherichia coli that facilitates the degradation of gamma-aminobutyrate (GABA) into succinate semialdehyde (UniProt: P22256). This enzyme is a key component of the GABA shunt, a metabolic pathway that bypasses certain steps of the tricarboxylic acid (TCA) cycle and allows the bacterium to utilize GABA as a primary source of carbon and nitrogen (PubMed: 15522865). While GABA-AT is a well-established therapeutic target in humans for the treatment of refractory epilepsy—where drugs like Vigabatrin act as irreversible inhibitors—the E. coli version serves as a model for studying aminotransferase mechanisms and bacterial stress responses (PubMed: 10411888). In the context of drug development, GabT is explored as a potential target for antimicrobial agents, as its inhibition can disrupt essential metabolic pathways in pathogenic strains (PubMed: 25631104). The enzyme's structure consists of a homodimer, with each subunit containing an active site that binds the PLP cofactor, making it susceptible to various suicide inhibitors and PLP-antagonists (PubMed: 11804418). The target name provided (U4-aminobutyrate aminotransferase) appears to contain a typographical error, as the standard nomenclature is 4-aminobutyrate aminotransferase.

Other names

GABA transaminaseGABA-AT4-aminobutyrate:2-oxoglutarate aminotransferaseGamma-amino-butyrate transaminaseGabTL-glutamate:4-aminobutyrate aminotransferase

Irreversible suicide inhibition via covalent modification of the pyridoxal phosphate (PLP) cofactor or the active site lysine residue, which prevents the transamination of GABA into succinate semialdehyde.