Adriana Chrenková, Francesco Bisiak, Ditlev E Brodersen
{"title":"Breaking bad nucleotides: understanding the regulatory mechanisms of bacterial small alarmone hydrolases.","authors":"Adriana Chrenková, Francesco Bisiak, Ditlev E Brodersen","doi":"10.1016/j.tim.2023.12.011","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23275,"journal":{"name":"Trends in Microbiology","volume":" ","pages":"769-780"},"PeriodicalIF":14.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.tim.2023.12.011","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/22 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Trends in Microbiology serves as a comprehensive, multidisciplinary forum for discussing various aspects of microbiology, spanning cell biology, immunology, genetics, evolution, virology, bacteriology, protozoology, and mycology. In the rapidly evolving field of microbiology, technological advancements, especially in genome sequencing, impact prokaryote biology from pathogens to extremophiles, influencing developments in drugs, vaccines, and industrial enzyme research.