Leppla S H
Proc Natl Acad Sci U S A. 1982 May;79(10):3162-6. doi: 10.1073/pnas.79.10.3162.
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.
保护性抗原（PA）、致死因子（LF）和水肿因子（EF）。这些蛋白质单独在动物体内不会引起已知的生理效应，但两两组合会产生两种毒性作用。将PA与LF注射到大鼠体内会在60分钟内导致其死亡，而将PA与EF注射到兔子和豚鼠的皮肤中会引起水肿。这些蛋白质的作用机制尚未确定。本文表明，EF是炭疽芽孢杆菌产生的一种无活性形式的腺苷酸环化酶[ATP焦磷酸裂解酶（环化），EC 4.6.1.1]。与热稳定的真核细胞物质接触后会发生激活。所产生的腺苷酸环化酶的比活性几乎与已知活性最高的环化酶相当。在中国仓鼠卵巢细胞中，暴露于PA和EF后，cAMP浓度会立即升高至比正常水平高约200倍的值，在毒素持续存在的情况下保持高位，去除毒素后迅速下降。cAMP的升高被过量的LF完全阻断。有人提出，PA与细胞相互作用形成一个受体系统，通过该系统EF以及可能还有LF能够进入细胞质。
