ArticleProceedings of the National Academy of Sciences of the United States of America2015
Catalytic mechanism and allosteric regulation of an oligomeric (p)ppGpp synthetase by an alarmone.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 125 citations in OpenAlex.
- Nanobody-mediated control of long RSH Rel and RelA catalysis by restriction of their conformational landscape.Nature communications · 2026Article
- Controlled Delivery and Light-Induced Release of Magic Spot Nucleotides in Escherichia coli.Angewandte Chemie (International ed. in English) · 2026Article
- Article
- Analysis of (p)ppGpp metabolism and signaling using a dynamic luminescent reporter.PLoS genetics · 2025Article
- A shared alarmone-GTP switch controls persister formation in bacteria.Nature microbiology · 2025Article
- Mechanisms of neutralization of toxSAS from toxin-antitoxin modules.Nature chemical biology · 2025Article
- Article
- Synthetase and Hydrolase Specificity Collectively Excludes 2'-Deoxyguanosine from Bacterial Alarmone.bioRxiv : the preprint server for biology · 2024Article
- Biochemical and X-ray analyses of the players involved in the faRel2/aTfaRel2 toxin-antitoxin operon.Acta crystallographica. Section F, Structural biology communications · 2023Article
- Functional Characterization of Small Alarmone Synthetase and Small Alarmone Hydrolase Proteins from Treponema denticola.Microbiology spectrum · 2023Article
- Sound the (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide pGpp.Infection and immunity · 2023Review
- Identification of a broadly conserved family of enzymes that hydrolyze (p)ppApp.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Review
- New perspectives on the molecular mechanisms of stress signalling by the nucleotide guanosine tetraphosphate (ppGpp), an emerging regulator of photosynthesis in plants and algae.The New phytologist · 2023Review
- The structure of DarB in complex with RelScience advances · 2023Article
- (p)ppGpp - an important player during heat shock response.microLife · 2023Review
- Role of (p)ppGpp in antibiotic resistance, tolerance, persistence and survival in Firmicutes.microLife · 2023Review
- (p)ppGpp and moonlighting RNases influence the first step of lipopolysaccharide biosynthesis inmicroLife · 2023Article
- Structural variations between small alarmone hydrolase dimers support different modes of regulation of the stringent response.The Journal of biological chemistry · 2022Article
- GGDEF domain as spatial on-switch for a phosphodiesterase by interaction with landmark protein HubP.NPJ biofilms and microbiomes · 2022Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleotide-based second messengers serve in the response of living organisms to environmental changes. In bacteria and plant chloroplasts, guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) [collectively named "(p)ppGpp"] act as alarmones that globally reprogram cellular physiology during various stress conditions. Enzymes of the RelA/SpoT homology (RSH) family synthesize (p)ppGpp by transferring pyrophosphate from ATP to GDP or GTP. Little is known about the catalytic mechanism and regulation of alarmone synthesis. It also is unclear whether ppGpp and pppGpp execute different functions. Here, we unravel the mechanism and allosteric regulation of the highly cooperative alarmone synthetase small alarmone synthetase 1 (SAS1) from Bacillus subtilis. We determine that the catalytic pathway of (p)ppGpp synthesis involves a sequentially ordered substrate binding, activation of ATP in a strained conformation, and transfer of pyrophosphate through a nucleophilic substitution (SN2) reaction. We show that pppGpp-but not ppGpp-positively regulates SAS1 at an allosteric site. Although the physiological significance remains to be elucidated, we establish the structural and mechanistic basis for a biological activity in which ppGpp and pppGpp execute different functional roles.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.