Isolation and characterization of the product of inactivation of γ-aminobutyric acid aminotransferase by gabaculine Original Research Article

Gabaculine (5-amino-1,3-cyclohexadienylcarboxylic acid, ), a naturally occurring neurotoxin isolated from Streptomyces toyocaenis, has been shown to be a mechanism-based inactivator of γ-aminobutyric acid aminotransferase (GABA-AT) (Rando, R. R. Biochemistry 1977, 16, 4604). Inactivation results from reaction of gabaculine with the pyridoxal 5′-phosphate (PLP) cofactor. Two HPLC systems for isolating this inactivator-PLP adduct are described as well as a detailed characterization of the adduct, including the ultraviolet–visible spectrum, electrospray mass spectra, and NMR spectrum. The same spectral characterization of the chemically synthesized gabaculine-PLP adduct is also reported.