consequences and utility of the zinc-dependent metalloprotease activity of anthrax lethal toxin后果和效用的zinc-dependent metalloprotease炭疽致命毒素的活性.pdfVIP

Toxins 2010, 2, 1038-1053; doi:10.3390/toxins2051038 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review Consequences and Utility of the Zinc-Dependent Metalloprotease Activity of Anthrax Lethal Toxin Jennifer Bromberg-White 1, Chih-Shia Lee 1,2 and Nicholas Duesbery 1,* 1 Laboratory of Cancer and Developmental Cell Biology, The Van Andel Research Institute, 333 Bostwick NE Grand Rapids, MI, 49503, USA; E-Mails: jenn.white @ (J.B.-W.); chihshia.lee@ (C.-S.L.) 2 Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing MI 48824, USA * Author to whom correspondence should be addressed; E-Mail: nick.duesbery@; Tel.: 616-234-5258; Fax: 616-234-5259. Received: 2 April 2010; in revised form: 29 April 2010 / Accepted: 5 May 2010 / Published: 11 May 2010 Abstract: Anthrax is caused by the gram-positive bacterium Bacillus anthracis . The pathogenesis of this disease is dependent on the presence of two binary toxins, edema toxin (EdTx) and lethal toxin (LeTx). LeTx, the major virulence factor contributing to anthrax, contains the effector moiety lethal factor (LF), a zinc-dependent metalloprotease specific for targeting mitogen-activated protein kinase kinases. This review will focus on the protease-specific activity and function of LF, and will include a discussion on the implications and consequences of this activity, both in terms of anthrax disease, and how this activity can be exploited to gain insight into other pathologic conditions. Ke