Document Detail


Molecular basis for the pharmacological actions of Clostridium botulinum type C2 toxin.
MedLine Citation:
PMID:  6236295     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The light chain of type C2 toxin produced by Clostridium botulinum was isolated by high-performance liquid chromatography. The protein eluted as a single peak; as judged by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, it had an apparent molecular weight of 51,000 daltons. The light chain was an enzyme that possessed ADP-ribosylating activity. In experiments with synthetic substrates (homo-poly-L-amino acids; alanine, arginine, asparagine, aspartic acid, histidine, leucine, lysine, methionine, phenylalanine, proline, serine and tryptophan), only poly-L-arginine was ADP-ribosylated by the enzyme. In experiments with endogenous substrates (50,000 X g pellet and 50,000 X g supernatant from homogenates of mouse brain, liver and lung), the enzyme ADP-ribosylated proteins or polypeptides in both the particulate and soluble fractions. ADP-ribosylation of the soluble substrate was antagonized by adenine (K1 approximately 2.1 X 10(-5) M) and by adenosine (K1 approximately 2.7 X 10(-4) M); the reaction was reversed by a large molar excess of nicotinamide (0.1 M). ADP-ribosylation of soluble substrate was diminished when the substrate had been pretreated with 1,2-cyclohexane-dione (0.1 M), a site reactive reagent that modified selectively arginine residues. Neither the light chain nor the heavy chain of the binary toxin possessed adenylate cyclase activity. Tissue fractions did possess endogenous adenylate cyclase activity, but the toxin did not stimulate this activity. The data indicate that the binary toxin produced by Clostridium botulinum resembles other protein toxins.
Authors:
L L Simpson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  230     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1984 Sep 
Date Detail:
Created Date:  1984-10-24     Completed Date:  1984-10-24     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  665-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenine / pharmacology
Adenosine / pharmacology
Adenosine Diphosphate Ribose / metabolism
Adenylate Cyclase / metabolism
Amino Acids / metabolism
Animals
Chromatography, High Pressure Liquid
Hot Temperature
Mice
Molecular Weight
Niacinamide / metabolism
Peptides / metabolism
Toxoids / pharmacology*
Grant Support
ID/Acronym/Agency:
NS-15409/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Clostridium botulinum toxoid; 0/Peptides; 0/Toxoids; 20762-30-5/Adenosine Diphosphate Ribose; 25212-18-4/polyarginine; 58-61-7/Adenosine; 73-24-5/Adenine; 98-92-0/Niacinamide; EC 4.6.1.1/Adenylate Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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