ArticleMolecular cell2015
Molecular mechanism and evolution of guanylate kinase regulation by (p)ppGpp.
Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 95 citations in OpenAlex.
- Bacterial growth rate in populations and single cells.Nature microbiology · 2026Review
- The alarmone pGpp inhibits translation through GTP depletion.Nucleic acids research · 2026Article
- Starvation-independent alarmone production inhibits translation through GTP depletion.bioRxiv : the preprint server for biology · 2026Article
- A shared alarmone-GTP switch controls persister formation in bacteria.Nature microbiology · 2025Article
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- Inactivation of guanylate kinase inHeliyon · 2024Article
- Environmental purines decrease Pseudomonas aeruginosa biofilm formation by disrupting c-di-GMP metabolism.Cell reports · 2024Article
- Protein-Ligand Interactions in Scarcity: The Stringent Response from Bacteria to Metazoa, and the Unanswered Questions.International journal of molecular sciences · 2023Review
- 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
- From magic spot ppGpp to MESH1: Stringent response from bacteria to metazoa.PLoS pathogens · 2023Article
- The many roles of cyclic di-AMP to control the physiology ofmicroLife · 2023Review
- GTPase Era at the heart of ribosome assembly.Frontiers in molecular biosciences · 2023Review
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- Diversity of mechanisms to control bacterial GTP homeostasis by the mutually exclusive binding of adenine and guanine nucleotides to IMP dehydrogenase.Protein science : a publication of the Protein Society · 2022Article
- Inhibition of SRP-dependent protein secretion by the bacterial alarmone (p)ppGpp.Nature communications · 2022Article
- Impact of the Stringent Stress Response on the Expression of Methicillin Resistance inAntibiotics (Basel, Switzerland) · 2022Article
- Diverse molecular mechanisms of transcription regulation by the bacterial alarmone ppGpp.Molecular microbiology · 2022Review
- The nucleotide messenger (p)ppGpp is an anti-inducer of the purine synthesis transcription regulator PurR in Bacillus.Nucleic acids research · 2022Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The nucleotide (p)ppGpp mediates bacterial stress responses, but its targets and underlying mechanisms of action vary among bacterial species and remain incompletely understood. Here, we characterize the molecular interaction between (p)ppGpp and guanylate kinase (GMK), revealing the importance of this interaction in adaptation to starvation. Combining structural and kinetic analyses, we show that (p)ppGpp binds the GMK active site and competitively inhibits the enzyme. The (p)ppGpp-GMK interaction prevents the conversion of GMP to GDP, resulting in GMP accumulation upon amino acid downshift. Abolishing this interaction leads to excess (p)ppGpp and defective adaptation to amino acid starvation. A survey of GMKs from phylogenetically diverse bacteria shows that the (p)ppGpp-GMK interaction is conserved in members of Firmicutes, Actinobacteria, and Deinococcus-Thermus, but not in Proteobacteria, where (p)ppGpp regulates RNA polymerase (RNAP). We propose that GMK is an ancestral (p)ppGpp target and RNAP evolved more recently as a direct target in Proteobacteria.
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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.