Journal ArticleDOI
Proteolytic Inactivation of MAP-Kinase-Kinase by Anthrax Lethal Factor
Nicholas S. Duesbery,Craig P. Webb,Stephen H. Leppla,Valery M. Gordon,Kurt Klimpel,Terry D. Copeland,Natalie G. Ahn,M Oskarsson,Kenji Fukasawa,Ken D. Paull,George F. Vande Woude +10 more
TLDR
It is shown that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 and that this cleavage inactivates MAPKK1 and inhibits the MAPK signal transduction pathway.Abstract:
Anthrax lethal toxin, produced by the bacterium Bacillus anthracis, is the major cause of death in animals infected with anthrax. One component of this toxin, lethal factor (LF), is suspected to be a metalloprotease, but no physiological substrates have been identified. Here it is shown that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 (MAPKK1 and MAPKK2) and that this cleavage inactivates MAPKK1 and inhibits the MAPK signal transduction pathway. The identification of a cleavage site for LF may facilitate the development of LF inhibitors.read more
Citations
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Drug design with a new transition state analog of the hydrated carbonyl: silicon-based inhibitors of the HIV protease
Chien-An Chen,Scott McN. Sieburth,Athanasios Glekas,Gregory W. Hewitt,George L. Trainor,Susan Erickson-Viitanen,Sena Garber,Beverly C Cordova,Susan Jeffry,Ronald M Klabe +9 more
TL;DR: In their first evaluation as inhibitors of an aspartic protease, silanediol peptidomimetics have been found to be nearly as potent as currently available pharmaceutical agents, in enzyme and cell protection assays, and provide a novel foundation for the design of therapeutic agents.
Journal ArticleDOI
Anthrax Protective Antigen Cleavage and Clearance from the Blood of Mice and Rats
TL;DR: The cell binding-independent cleavage of PA was verified by using Ub-PA to rescue mice from toxin challenge by competitively binding circulating LF and it was shown that lethality of LF for mice after PA was no longer measurable in circulation, suggesting active PA sequestration at tissue surfaces.
Journal ArticleDOI
Potent inhibitors of anthrax lethal factor from green tea
Isabella Dell'Aica,Massimo Donà,Fiorella Tonello,Alejandro Piris,Michèle Mock,Cesare Montecucco,Spiridione Garbisa +6 more
TL;DR: The properties of some polyphenols contained in green tea as powerful inhibitors of LF metalloproteolytic activity are described, and how the main catechin of green tea, (−)epigallocatechin‐3‐gallate, prevents the LF‐induced death of macrophages and Fischer 344 rats.
Journal ArticleDOI
Spores and soil from six sides: interdisciplinarity and the environmental biology of anthrax (Bacillus anthracis).
Colin J. Carlson,Colin J. Carlson,Wayne M. Getz,Wayne M. Getz,Kyrre Kausrud,Carrie A. Cizauskas,Jason K. Blackburn,Fausto Bustos Carrillo,Rita R. Colwell,Rita R. Colwell,W. Ryan Easterday,Holly H. Ganz,Pauline L. Kamath,Ole Andreas Økstad,Wendy C. Turner,Anne-Brit Kolstø,Nils Christian Stenseth +16 more
TL;DR: Challenges of studying environmental transmission and persistence with a six‐sided interdisciplinary review of the biology of anthrax are identified, and how anthrax dynamics are shaped at the smallest scale by population genetics and interactions within the bacterial communities up to the broadest scales of ecosystem structure is discussed.
Journal ArticleDOI
Bacterial Toxins as Pathogen Weapons Against Phagocytes
Ana do Vale,Ana do Vale,Didier Cabanes,Didier Cabanes,Sandra Maria Zákia Lian Sousa,Sandra Maria Zákia Lian Sousa +5 more
TL;DR: This review will concentrate on toxins from Gram-positive and Gram-negative bacteria that manipulate cell signaling or induce cell death by either imposing direct damage to the host cells cytoplasmic membrane or enzymatically modifying key eukaryotic targets.
References
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Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells.
TL;DR: It is shown here that EF is an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1] produced by Bacillus anthracis in an inactive form and nearly equals that of the most active known cyclase.
Journal ArticleDOI
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Michael A. White,Charles Nicolette,Audrey Minden,Anthony Polverino,Linda Van Aelst,Michael Karin,Michael Wigler +6 more
TL;DR: Results indicate that multiple cellular components, including Raf1, are activated by Ha-Ras and contribute to Ha- Ras-induced mammalian cell transformation.