The pyridoxal-5-phosphate (PLP) effector pathway is involved in the catabolism of γ-aminobutyric acid (GABA) and is regulated by the transcriptional activator GabR. PLP, the active form of vitamin B6, serves as a cofactor for GabR, enabling it to control expression of genes required for GABA utilization. Bacillus subtilis GabR is a transcriptional regulator consisting of a helix-turn-helix N-terminal DNA-binding domain, a pyridoxal 5'-phosphate (PLP)-binding C-terminal domain that has a structure homologous to aminotransferases, and a linker of 29 amino acid residues. In the presence of γ-aminobutyrate (GABA), GabR activates the transcription of gabT and gabD, which encode GABA aminotransferase and succinate semialdehyde dehydrogenase, respectively. GabR is a PLP-dependent transcription factor of the MocR/GabR family. It binds to the promoter region of GABA catabolic genes and activates their transcription in response to GABA and PLP availability. This regulation ensures that GABA metabolism is induced only when both substrate (GABA) and cofactor (PLP) are present. Key genes in the GabR regulog include: gabT – Encodes GABA transaminase, a PLP-dependent enzyme that catalyzes the conversion of GABA to succinate semialdehyde, linking GABA catabolism to the TCA cycle. gabP – Encodes a GABA permease, responsible for importing GABA into the cell for metabolism. gabD – Encodes succinate semialdehyde dehydrogenase, which converts succinate semialdehyde into succinate, a direct intermediate of the TCA cycle.

Pyridoxal-5-phosphate References