Botulinum Neurotoxin A Protease: Discovery of Natural Product Exosite Inhibitors

被引：41

作者：

Silhar, Peter ^{[1
,2
]}

Capkova, Katerina ^{[1
,2
]}

Salzameda, Nicholas T. ^{[1
,2
]}

Barbieri, Joseph T. ^{[3
]}

Hixon, Mark S. ^{[4
]}

Janda, Kim D. ^{[1
,2
,5
]}

机构：

[1] Scripps Res Inst, Skaggs Inst Chem Biol, Dept Chem, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Skaggs Inst Chem Biol, Dept Immunol, La Jolla, CA 92037 USA

[3] Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA

[4] Takeda San Diego Inc, Discovery Biol, San Diego, CA 92121 USA

[5] Scripps Res Inst, WIRM, La Jolla, CA 92037 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2010年 / 132卷 / 09期

基金：

美国国家卫生研究院;

关键词：

SMALL-MOLECULE INHIBITORS; SUBSTRATE RECOGNITION; SEROTYPE-A; IDENTIFICATION; CHEMISTRY;

D O I：

10.1021/ja910761y

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 compounds found In Echinacea, 13 and 14, were also inhibitors of the protease.

引用

页码：2868 / +

页数：5

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