Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells.
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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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Journal ArticleDOI
Antidotes to anthrax lethal factor intoxication. Part 3: Evaluation of core structures and further modifications to the C2-side chain.
Guan-Sheng Jiao,Seongjin Kim,Mahtab Moayeri,Devorah Crown,April Thai,Lynne Cregar-Hernandez,Linda McKasson,Banumathi Sankaran,Axel T. Lehrer,Teri Wong,Lisa Johns,Stephen A. Margosiak,Stephen H. Leppla,Alan T. Johnson +13 more
TL;DR: Four core structures capable of providing sub-nanomolar inhibitors of anthrax lethal factor (LF) were evaluated by comparing the potential for toxicity, physicochemical properties, in vitro ADME profiles, and relative efficacy in a rat lethal toxin (LT) model of LF intoxication.
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Uptake of binary actin ADP-ribosylating toxins.
TL;DR: The focus of this article is on the cellular uptake mechanism of the family of binary actin ADP-ribosylating toxins from clostridia, which leads to a complete depolymerization of the actin filaments and, thereby, to rounding up of cultured cells.
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Effects of 39 Compounds on Calmodulin-Regulated Adenylyl Cyclases AC1 and Bacillus anthracis Edema Factor.
Carolin Lübker,Roland Seifert +1 more
TL;DR: CaM- Stimulated AC1 activity is more insensitive to inhibition by small molecules than CaM-stimulated EF activity, which indicates that inhibition of AC1 and EF by calmidazolium chloride is largely mediated via a Cam-independent allosteric mechanism.
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Selection and evaluation of the immunogenicity of protective antigen mutants as anthrax vaccine candidates
TL;DR: This study demonstrates that PA-based vaccines could be improved both in terms of safety and efficacy by strategic mutations that not only render PA non-functional but also simultaneously enhance its immunogenic potency.
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