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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Quantum mechanical/molecular mechanical study of anthrax lethal factor catalysis
TL;DR: In this paper, a hybrid quantum mechanical and molecular mechanical study of the catalysis of anthrax lethal factor was carried out and it was shown that the zinc peptidase uses the same general base-general acid mechanism as in thermolysin and carboxypeptidase A, in which a zinc-bound water is activated by Glu687 to nucleophilically attack the scissile carbonyl carbon in the substrate.
Journal ArticleDOI
Implication of pH in the catalytic properties of anthrax lethal factor.
TL;DR: It is presented the first evidence that additional metal ions are required for the LF catalyzed hydrolysis of native substrate, and that the pH alteration causes a significant change of catalytic properties of LF.
Journal ArticleDOI
Combinatory action of VEGFR2 and MAP kinase pathways maintains endothelial-cell integrity
Hanbing Zhong,Danyang Wang,Nan Wang,Yesenia Ríos,Haigen Huang,Song Li,Xinrong Wu,Shuo Lin,Shuo Lin +8 more
TL;DR: This is the first study to elucidate the pathways controlling maintenance of endothelial Integrity using a chemical genetics approach, indicating that endothelial integrity is controlled by the combined action of the VEGFR2 and MAP kinase pathways.
Journal ArticleDOI
NMR conformational properties of an Anthrax Lethal Factor domain studied by multiple amino acid-selective labeling.
Dionysios J. Vourtsis,Christos T. Chasapis,George Pairas,Detlef Bentrop,Georgios A. Spyroulias +4 more
TL;DR: This work presents the successful overexpression of a polypeptide of 233 residues, corresponding to the structured part of the N-terminal domain of Anthrax Lethal Factor, using Escherichia coli expression system.
Journal ArticleDOI
PAK in pathogen-host interactions
TL;DR: Examples of modulation of PAK activity in human cells by both intracellular and extracellular pathogens are presented, focusing on one eukaryotic pathogen, the human malaria parasite Plasmodium falciparum, and two Gram-negative bacteria.
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
Multiple Ras functions can contribute to mammalian cell transformation.
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.