Identification of gangliosides as inhibitors of ADP-ribosyltransferases of pertussis toxin and exoenzyme C3 from Clostridium botulinum.
We have previously reported the presence of an endogenous inhibitory activity in bovine brain for the ADP-ribosylation of GTP-binding proteins catalyzed by pertussis toxin (PT) (Hara-Yokoyama, M., and Furuyama, S. (1989) Biochem. Biophys. Res. Commun. 160, 67-71). In the present study, we identified the inhibitor as a ganglioside. The screening of various gangliosides revealed that GQ1b alpha most effectively inhibited the ADP-ribosyltransferase activities of both the holoenzyme and the catalytic subunit of PT. GQ1b alpha is a ganglioside newly identified as one of the antigens recognized by the cholinergic neuron-specific antibody, anti-Chol-1 alpha (Hirabayashi, Y., Nakao, T., Irie, F., Whittaker, V.P., Kon, K., and Ando, S. (1992) J. Biol. Chem. 267, 12973-12978). GQ1b alpha also inhibited the PT-catalyzed NAD+ glycohydrolysis. Unlike PT activity, the ADP-ribosylation and the NAD+ glycohydrolysis catalyzed by the C3 exoenzyme from Clostridium botulinum type C were inhibited by GT1b and GQ1b. The ADP-ribosylation catalyzed by either PT or the C3 exoenzyme was not inhibited by ceramide, galactocerebroside, or sialic acid. In addition to the inhibitory action of gangliosides on ADP-ribosylation, the importance of gangliosides as regulators of NAD+ metabolism is discussed.
Hara-Yokoyama
M
M
Department of Physiology, Nihon University School of Dentistry at Matsudo, Japan.
Hirabayashi
Y
Y
Irie
F
F
Syuto
B
B
Moriishi
K
K
Sugiya
H
H
Furuyama
S
S
D036002:ADP Ribose Transferases / Q000378:metabolism*; D000818:Animals; D001905:Botulinum Toxins; D001921:Brain / Q000378:metabolism; D002240:Carbohydrate Sequence; D002384:Catalysis; D002417:Cattle; D002518:Ceramides / Q000494:pharmacology; D019826:Cholic Acid; D002793:Cholic Acids / Q000378:metabolism; D005699:Galactosylceramides / Q000494:pharmacology; D005732:Gangliosides / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid; D037342:Pertussis Toxin; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012794:Sialic Acids / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000378:metabolism*
D002518:Ceramides; D002793:Cholic Acids; D005699:Galactosylceramides; D005732:Gangliosides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012794:Sialic Acids; D010566:Virulence Factors, Bordetella; C002454:galactocerebroside; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D037342:Pertussis Toxin; D001905:Botulinum Toxins; D019826:Cholic Acid; D019158:N-Acetylneuraminic Acid