Document Detail


Botulinum neurotoxin A protease: discovery of natural product exosite inhibitors.
MedLine Citation:
PMID:  20158239     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A new mechanistic class of BoNT/A zinc metalloprotease inhibitors, from Echinacea, exemplified by the natural product d-chicoric acid (I1) is disclosed. A detailed evaluation of chicoric acid's mechanism of inhibition reveals that the inhibitor binds to an exosite, displays noncompetitive partial inhibition, and is synergistic with a competitive active site inhibitor when used in combination. Other components found in Echinacea, I3 and I4, were also inhibitors of the protease.
Authors:
Peter Silhár; Katerina Capková; Nicholas T Salzameda; Joseph T Barbieri; Mark S Hixon; Kim D Janda
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  132     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-03     Completed Date:  2010-06-14     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2868-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Biological Factors / chemical synthesis,  chemistry,  pharmacology*
Botulinum Toxins, Type A / antagonists & inhibitors*,  metabolism
Caffeic Acids / chemical synthesis,  chemistry,  pharmacology
Chlorogenic Acid / chemical synthesis,  chemistry,  pharmacology
Clostridium botulinum / enzymology*
Hydroxamic Acids / chemical synthesis,  chemistry,  pharmacology
Molecular Conformation
Phenols / chemical synthesis,  chemistry,  pharmacology
Protease Inhibitors / chemical synthesis,  chemistry,  pharmacology*
Stereoisomerism
Structure-Activity Relationship
Succinates / chemical synthesis,  chemistry,  pharmacology
Grant Support
ID/Acronym/Agency:
N01 AI030050/AI/NIAID NIH HHS; N01-AI080671/AI/NIAID NIH HHS; N01-AI30050/AI/NIAID NIH HHS; R01 AI080671/AI/NIAID NIH HHS; R01 AI080671-01A1/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Biological Factors; 0/Caffeic Acids; 0/Hydroxamic Acids; 0/Phenols; 0/Protease Inhibitors; 0/Succinates; 0/caftaric acid; 318ADP12RI/Chlorogenic Acid; 70831-56-0/chicoric acid; EC 3.4.24.69/Botulinum Toxins, Type A
Comments/Corrections

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