Isolation and characterization of the product of inactivation of gamma-aminobutyric acid aminotransferase by gabaculine.
Gabaculine (5-amino-1,3-cyclohexadienylcarboxylic acid, 1), a naturally occurring neurotoxin isolated from Streptomyces toyocaenis, has been shown to be a mechanism-based inactivator of gamma-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.
Fu
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Department of Chemistry, Northwestern University, Evanston, IL 60208-3113, USA.
Silverman
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D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D007700:Kinetics; D013057:Spectrum Analysis; D013552:Swine
D003509:Cyclohexanecarboxylic Acids; C012987:gabaculine; D000612:4-Aminobutyrate Transaminase