Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells.
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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.read more
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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.
Journal Article
Radioimmunoassay of cyclic AMP and cyclic GMP.
Journal ArticleDOI
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.
Journal ArticleDOI
Activation of adenylate cyclase by choleragen.
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.
Journal ArticleDOI
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.