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Open AccessJournal ArticleDOI

Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells.

Stephen H. Leppla
- 01 May 1982 - 
- Vol. 79, Iss: 10, pp 3162-3166
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TLDR
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.
Abstract
Anthrax toxin is composed of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). These proteins individually cause no known physiological effects in animals but in pairs produce two toxic actions. Injection of PA with LF causes death of rats in 60 min, whereas PA with EF causes edema in the skin of rabbits and guinea pigs. The mechanisms of action of these proteins have not been determined. It is shown here that EF is an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] produced by Bacillus anthracis in an inactive form. Activation occurs upon contact with a heat-stable eukaryotic cell material. The specific activity of the resulting adenylate cyclase nearly equals that of the most active known cyclase. In Chinese hamster ovary cells exposed to PA and EF, cAMP concentrations increase without a lag to values about 200-fold above normal, remain high in the continued presence of toxin, and decrease rapidly after its removal. The increase in cAMP is completely blocked by excess LF. It is suggested that PA interacts with cells to form a receptor system by which EF and perhaps LF gain access to the cytoplasm.

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Book ChapterDOI

Defense Against Biological Weapons (Biodefense)

TL;DR: Biological warfare (germ warfare) is defined as the use of any disease-causing organism or toxin(s) found in nature as weapons of war with the intent to destroy an adversary.
Journal ArticleDOI

MD Simulations of Anthrax Edema Factor: Calmodulin Complexes with Mutations in the Edema Factor “Switch A” Region and Docking of 3′-deoxy ATP into the Adenylyl Cyclase Active Site of Wild-Type and Mutant Edema Factor Variants

TL;DR: Results of molecular dynamics simulations on two EF:CaM complexes, one containing wild-type EF and the other containing EF in which a cluster of residues in the switch A region have been mutated to alanine indicate the importance of the mutated switch A residues in maintaining a compact EF: CaM complex that appears to be a prerequisite for the generation of a fully-functional adenylyl cyclase active site.
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Evaluation of the ability of N-terminal fragment of lethal factor of Bacillus anthracis for delivery of Mycobacterium T cell antigen ESAT-6 into cytosol of antigen presenting cells to elicit effective cytotoxic T lymphocyte response.

TL;DR: In vitro Th1 cytokines data and CTL assay proved that efficient delivery of LFn can be used to deliver multiepitopes of T cells or multiproteins which can generate effective CTLs against intracellular pathogens like M. tuberculosis.
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Purification of VBacillus anthracis lethal factor by immunosorbent chromatography

TL;DR: The antigen-antibody complex was found to undergo a reversible dissociation at moderately high pH values, and the ionizable group(s) responsible for this dissociation exhibited a pKa value of 9.90.
References
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Journal Article

Protein Measurement with the Folin Phenol Reagent

TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
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Restoration of Several Morphological Characteristics of Normal Fibroblasts in Sarcoma Cells Treated with Adenosine-3':5'-Cyclic Monophosphate and Its Derivatives

TL;DR: The data suggest that cyclic AMP may be an important factor in the determination of morphology of normal fibroblasts and this function may be lost or altered during transformation.
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Activation of adenylate cyclase by choleragen.

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TL;DR: An attempt is made to evaluate the mechanism of action of NAD Glycohydrolase and ADP-Ribosyltransferase on GTP-Binding Protein and GTPase Activity in response to the presence of Gangliosides and Their Oligosaccharides in Choleragen.
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A Permeability Factor (Toxin) found in Cholera Stools and Culture Filtrates and its Neutralization by Convalescent Cholera Sera.

TL;DR: A Permeability Factor (Toxin) found in Cholera Stools and Culture Filtrates and its Neutralization by Convalescent CholERA Sera is found to be neutralized by convalescent cholera patients.
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