ArticleMolecular cell2020
ppGpp Coordinates Nucleotide and Amino-Acid Synthesis in E. coli During Starvation.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61 citing papers in PubMed, 96 citations in OpenAlex.
- Bacterial growth rate in populations and single cells.Nature microbiology · 2026Review
- 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
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- ppGpp regulates transcription elongation via direct and indirect inputs to RNA polymerase pausing and nucleotide addition.bioRxiv : the preprint server for biology · 2026Article
- Metabolic responses to benzoic acid stress and glutamine transport-dependent vulnerabilities in Escherichia coli revealed by NMR metabolomics.World journal of microbiology & biotechnology · 2026Article
- Mike Cashel: magic spot magician.Journal of bacteriology · 2026Article
- A phosphohistidine phosphatase promotes starvation survival by dephosphorylating nucleoside diphosphate kinase.Cell reports · 2026Article
- Species-level profiling ofPeerJ · 2026Article
- Dissection of amino acid acquisition pathways demonstrates that amino acid starvation of Borrelia burgdorferi results in a (p)ppGpp-independent maladaptive response.Communications biology · 2025Article
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- The stringent response does not influence ribosome pausing in Bacillus subtilis.Nucleic acids research · 2025Article
- Using BONCAT to dissect the proteome ofmSphere · 2025Article
- Ribose-5-phosphate metabolism protectsmBio · 2025Article
- Salmonella stress response systems as targets for anti-virulence strategies.BMC microbiology · 2025Article
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- c-di-GMP inhibits rRNA methylation and impairs ribosome assembly in the presence of kanamycin.EMBO reports · 2025Article
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- Mini Bubble Columns for Miniaturizing Scale-Down.Engineering in life sciences · 2025Article
1 more citing papers are in PubMed but not listed here.
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3 authors at 2 institutions in 1 country.
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Abstract
(p)ppGpp is a nucleotide messenger universally produced in bacteria following nutrient starvation. In E. coli, ppGpp inhibits purine nucleotide synthesis by targeting several different enzymes, but the physiological significance of their inhibition is unknown. Here, we report the structural basis of inhibition for one target, Gsk, the inosine-guanosine kinase. Gsk creates an unprecedented, allosteric binding pocket for ppGpp by restructuring terminal sequences, which restrains conformational dynamics necessary for catalysis. Guided by this structure, we generated a chromosomal mutation that abolishes Gsk regulation by ppGpp. This mutant strain accumulates abnormally high levels of purine nucleotides following amino-acid starvation, compromising cellular fitness. We demonstrate that this unrestricted increase in purine nucleotides is detrimental because it severely depletes pRpp and essential, pRpp-derived metabolites, including UTP, histidine, and tryptophan. Thus, our results reveal the significance of ppGpp's regulation of purine nucleotide synthesis and a critical mechanism by which E. coli coordinates biosynthetic processes during starvation.
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