Botulinum neurotoxin A protease: discovery of natural product exosite inhibitors. J Am Chem Soc 2010 Mar 10;132(9):2868-9
Date
02/18/2010Pubmed ID
20158239Pubmed Central ID
PMC2832098DOI
10.1021/ja910761yScopus ID
2-s2.0-77950343388 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
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.
Author List
Silhár P, Capková K, Salzameda NT, Barbieri JT, Hixon MS, Janda KDAuthor
Joseph T. Barbieri PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Biological FactorsBotulinum Toxins, Type A
Caffeic Acids
Chlorogenic Acid
Clostridium botulinum
Hydroxamic Acids
Molecular Conformation
Phenols
Protease Inhibitors
Stereoisomerism
Structure-Activity Relationship
Succinates