Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, DK-8000 Aarhus C, Denmark.
Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, DK-8000 Aarhus C, Denmark.
Trends Microbiol. 2024 Aug;32(8):769-780. doi: 10.1016/j.tim.2023.12.011. Epub 2024 Jan 22.
Guanosine tetra- and pentaphosphate nucleotides, (p)ppGpp, function as central secondary messengers and alarmones in bacterial cell biology, signalling a range of stress conditions, including nutrient starvation and exposure to cell-wall-targeting antibiotics, and are critical for survival. While activation of the stringent response and alarmone synthesis on starved ribosomes by members of the RSH (Rel) class of proteins is well understood, much less is known about how single-domain small alarmone synthetases (SASs) and their corresponding alarmone hydrolases, the small alarmone hydrolases (SAHs), are regulated and contribute to (p)ppGpp homeostasis. The substrate spectrum of these enzymes has recently been expanded to include hyperphosphorylated adenosine nucleotides, suggesting that they take part in a highly complex and interconnected signalling network. In this review, we provide an overview of our understanding of the SAHs and discuss their structure, function, regulation, and phylogeny.
鸟苷四磷酸和五磷酸核苷酸，（p）ppGpp，作为细菌细胞生物学中的中心二级信使和警报素发挥作用，信号传递一系列应激条件，包括营养饥饿和暴露于细胞壁靶向抗生素，并对生存至关重要。虽然由 RSH（Rel）类蛋白质成员激活饥饿核糖体上的严格反应和警报素合成已经得到很好的理解，但对于单结构域小分子警报素合成酶（SAS）及其相应的警报素水解酶，小分子警报素水解酶（SAH）如何被调节以及如何有助于（p）ppGpp 动态平衡的了解要少得多。这些酶的底物谱最近已扩展到包括高磷酸化的腺苷核苷酸，这表明它们参与了一个高度复杂和相互关联的信号网络。在这篇综述中，我们提供了对 SAH 的理解概述，并讨论了它们的结构、功能、调节和系统发育。
