REGULATION OF CYCLIC NUCLEOTIDE METABOLISM

鸟嘌呤核苷酸结合蛋白是许多信号的关键元件 动物细胞中的转导和代谢途径。其中一种蛋白质， ADP-核糖化因子是基于其增强体内 GTP的存在，霍乱毒素的ADP-核糖基转移酶活性， 一种被认为在霍乱发病机制中起重要作用的反应。这些 研究结果与ARF作为一种 毒素的变构激活剂。更详细地研究……的影响 在大肠杆菌中合成了一种重组蛋白ADP-核糖化因子。 重组ARF具有高亲和力的鸟嘌呤核苷酸结合和 刺激霍乱毒素ADP-核糖基转移酶和E. 大肠杆菌不耐热肠毒素LT-I、LT-IIA和11 LT-IIB。大肠埃希菌 不耐热的肠毒素以前被证明可以催化酶 与霍乱毒素的反应相似，并对 目标组织。霍乱毒素和大肠杆菌毒素表现出相当大的 结构上的保守，特别是在催化亚基上。这些 研究结果与结论是一致的，既有催化活性 而变构部位在毒素中是保守的。

Guanine nucleotide-binding proteins are critical elements in many signal transducing and metabolic pathways in animal cells. One of these proteins, ADP-ribosylation factor, was identified based on its ability to enhance, in the presence of GTP, the ADP-ribosyltransferase activity of cholera toxin, a reaction believed to be important in the pathogenesis of cholera. These studies were consistent with the conclusion that ARF serves as an allosteric activator of the toxin. To study in more detail the effects of ADP-ribosylation factor, a recombinant protein was synthesized in E. coli. The recombinant ARF exhibited high affinity guanine nucleotide-binding and stimulated the ADP-ribosyltransferase activities of cholera toxin and E. coli heat-labile enterotoxins LT-I, LT-IIA and 11 LT-IIB. The E. coli heat-labile enterotoxins were previously shown to catalyze enzymatic reactions similar to those of cholera toxin and to have similar effects on target tissues. Cholera toxin and the E. coli toxins exhibit considerable conservation in structure, particularly in the catalytic subunit. These studies are consistent with the conclusion that both the catalytic activity and the allosteric sites are conserved in the toxins.