ArticleNature chemical biology2019
Affinity-based capture and identification of protein effectors of the growth regulator ppGpp.
Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 123 papers.
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Who cites it
123 citing papers in PubMed.
- GTP hydrolysis-powered zinc metallochaperones as molecular switches.Current opinion in chemical biology · 2026Review
- Bacterial growth rate in populations and single cells.Nature microbiology · 2026Review
- The alarmone pGpp inhibits translation through GTP depletion.Nucleic acids research · 2026Article
- Phage portal proteins counteract stringent-response-mediated restriction.Nature communications · 2026Article
- Sustained ppGpp production underpins months-long survival of a bacterium in growth arrest.mBio · 2026Article
- Short autoinhibitory sequences control phase separation of an essential bacterial transcription termination factor.The EMBO journal · 2026Article
- ppGpp regulates transcription elongation via direct and indirect inputs to RNA polymerase pausing and nucleotide addition.bioRxiv : the preprint server for biology · 2026Article
- Adaptive metabolic rewiring and ion homeostasis enhance oxidative stress resistance inApplied and environmental microbiology · 2026Article
- Enzymatic activity of PBP1B is required for growth rate-independent ppGpp-mediated resistance to PBP2 inhibitors inJournal of bacteriology · 2026Article
- Starvation-independent alarmone production inhibits translation through GTP depletion.bioRxiv : the preprint server for biology · 2026Article
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- Functional interplay between (p)ppGpp and RNAP in Acinetobacter baumannii.PLoS pathogens · 2025Article
- Recent advances in metabolic engineering of Escherichia coli for riboflavin biosynthesis.World journal of microbiology & biotechnology · 2025Review
- A shared alarmone-GTP switch controls persister formation in bacteria.Nature microbiology · 2025Article
- In the shadow of antibiotics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nucleotide-induced hyper-oligomerization inactivates transcription termination factor ρ.Nature communications · 2025Article
- Antibiotic-associated changes in Akkermansia muciniphila alter its effects on host metabolic health.Microbiome · 2025Article
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- Temperature changes are signaled in cyanobacteria through the PipX interaction network.Frontiers in microbiology · 2025Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
Abstract
The nucleotide ppGpp is a highly conserved regulatory molecule in bacteria that helps tune growth rate to nutrient availability. Despite decades of study, how ppGpp regulates growth remains poorly understood. Here, we developed and validated a capture-compound mass spectrometry approach that identified >50 putative ppGpp targets in Escherichia coli. These targets control many key cellular processes and include 13 enzymes required for nucleotide synthesis. We demonstrated that ppGpp inhibits the de novo synthesis of all purine nucleotides by directly targeting the enzyme PurF. By solving a structure of PurF bound to ppGpp, we designed a mutation that ablates ppGpp-based regulation, leading to dysregulation of purine-nucleotide synthesis following ppGpp accumulation. Collectively, our results provide new insights into ppGpp-based growth control and a nearly comprehensive set of targets for future exploration. The capture compounds developed should also enable the rapid identification of ppGpp targets in any species, including pathogens.
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Registered trials
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.