Bifunctional Rel stringent factors, the most abundant class of RelA/SpoT homologs, are ribosome-associated enzymes that transfer a pyrophosphate from ATP onto the 3' of guanosine tri-/diphosphate (GTP/GDP) to synthesize the bacterial alarmone (p)ppGpp, and also catalyze the 3' pyrophosphate hydrolysis to degrade it. The regulation of the opposing activities of Rel enzymes is a complex allosteric mechanism that remains an active research topic despite decades of research. We show that a guanine-nucleotide-switch mechanism controls catalysis by Thermus thermophilus Rel (RelTt). The binding of GDP/ATP opens the N-terminal catalytic domains (NTD) of RelTt (RelTtNTD) by stretching apart the two catalytic domains. This activates the synthetase domain and allosterically blocks hydrolysis. Conversely, binding of ppGpp to the hydrolase domain closes the NTD, burying the synthetase active site and precluding the binding of synthesis precursors. This allosteric mechanism is an activity switch that safeguards against futile cycles of alarmone synthesis and degradation.

中文翻译：

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核苷酸转换机制介导Rel酶的相反催化活性。

双功能Rel严格因子是RelA / SpoT同源物中最丰富的一类，是与核糖体相关的酶，可将焦磷酸从ATP转移到鸟苷三/二磷酸鸟苷（GTP / GDP）的3'上，从而合成细菌警报蛋白（p）ppGpp ，并催化3'焦磷酸盐水解以使其降解。Rel酶的相反活性的调节是一个复杂的变构机制，尽管有数十年的研究，但仍是一个活跃的研究主题。我们显示鸟嘌呤核苷酸开关机制控制由嗜热栖热菌（RelTt）催化。GDP / ATP的结合通过拉开两个催化结构域来打开RelTt的N末端催化结构域（RelTtNTD）。这激活了合成酶结构域并变构地阻止了水解。反过来，ppGpp与水解酶结构域的结合会封闭NTD，掩埋合成酶的活性位点，并阻止合成前体的结合。这种变构机制是一种活动开关，可防止徒劳的警报合成和降解循环。