ADP-ribosylation by type C1 and D botulinum neurotoxins: stimulation by guanine nucleotides and inhibition by guanidino-containing compounds.
We recently reported that type D botulinum neurotoxin ADP-ribosylates a specific protein of Mr 21,000 in membrane fractions of various tissues (Ohashi, Y. and Narumiya, S. (1987) J. Biol. Chem. in press). We examined similar enzyme activities in other types (types A, B, C1 and E) of botulinum neurotoxins. Of these, only type C1 toxin showed the activity similar to type D toxin and ADP-ribosylated the same Mr 21,000 protein in membranes of mouse brain. No enzyme activities were detected in type A, B and E toxins under the present experimental conditions. GTP stimulated ADP-ribosylation by the two toxins in a concentration dependent manner from 10 nM to 100 microM. The maximum stimulation was about 6 fold. GDP was 10 times less potent than GTP and achieved similar maximum at 1 mM, while GMP, ADP and ATP had little effect. Several guanidino-containing compounds dose-dependently inhibited the activities of both toxins. The IC50 values were 8.5, 14.5 and 45 mM for agmatine, L-arginine methyl ester and guanidine, respectively.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000376:Agmatine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001905:Botulinum Toxins / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology*; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006153:Guanosine Diphosphate / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D051379:Mice; D008970:Molecular Weight; D014121:Toxoids / Q000378:metabolism*
C035415:Clostridium botulinum toxoid; D006146:Guanidines; D006150:Guanine Nucleotides; D014121:Toxoids; D006153:Guanosine Diphosphate; D000246:Adenosine Diphosphate Ribose; C026512:arginine methyl ester; D000376:Agmatine; D006160:Guanosine Triphosphate; D001120:Arginine; D001905:Botulinum Toxins