ArticleJournal of bacteriology2002
Intramolecular regulation of the opposing (p)ppGpp catalytic activities of Rel(Seq), the Rel/Spo enzyme from Streptococcus equisimilis.
Article in Journal of bacteriology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
97 citing papers in PubMed, 177 citations in OpenAlex.
- Sustained ppGpp production underpins months-long survival of a bacterium in growth arrest.mBio · 2026Article
- Structural Basis of pppGpp Binding to the N-Terminal Domain of the Bifunctional RelA/SpoT Homolog RelInternational journal of molecular sciences · 2026Article
- Nanobody-mediated control of long RSH Rel and RelA catalysis by restriction of their conformational landscape.Nature communications · 2026Article
- The N-Terminal Extension of theAntibiotics (Basel, Switzerland) · 2025Article
- Structural and Evolutionary Analysis of Proteins Endowed with a Nucleotidyltransferase, or Non-canonical Palm, Catalytic Domain.Journal of molecular evolution · 2024Article
- C-terminal deletion of RelA protein is suggested as a possible cause of infective endocarditis recurrence withAntimicrobial agents and chemotherapy · 2024Article
- Functional Characterization of Small Alarmone Synthetase and Small Alarmone Hydrolase Proteins from Treponema denticola.Microbiology spectrum · 2023Article
- Starvation sensing by mycobacterial RelA/SpoT homologue through constitutive surveillance of translation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Sound the (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide pGpp.Infection and immunity · 2023Review
- Protein-Ligand Interactions in Scarcity: The Stringent Response from Bacteria to Metazoa, and the Unanswered Questions.International journal of molecular sciences · 2023Review
- The structure of DarB in complex with RelScience advances · 2023Article
- Structural variations between small alarmone hydrolase dimers support different modes of regulation of the stringent response.The Journal of biological chemistry · 2022Article
- New Chemotypes for the Inhibition of (p)ppGpp Synthesis in the Quest for New Antimicrobial Compounds.Molecules (Basel, Switzerland) · 2022Article
- Genome-Wide Investigation of Pasteurella multocida Identifies the Stringent Response as a Negative Regulator of Hyaluronic Acid Capsule Production.Microbiology spectrum · 2022Article
- Unique Features of Alarmone Metabolism in Clostridioides difficile.Journal of bacteriology · 2022Article
- Awakening sleeper cells: a narrative review on bacterial magic spot synthetases as potential drug targets to overcome persistence.Current genetics · 2022Review
- Mutations inFrontiers in microbiology · 2022Article
- The Alarmone (p)ppGpp Regulates Primer Extension by Bacterial Primase.Journal of molecular biology · 2021Article
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37 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Catalytic and regulatory domains of the Rel/Spo homolog of Streptococcus equisimilis affecting (p)ppGpp synthesis and degradation activities have been defined, and opposing activities of the purified protein and its fragments have been compared. Two major domains of the 739-residue Rel(Seq) protein are defined by limited proteolytic digestion. In vitro assays of the purified N-terminal half-protein reveal synthesis of (p)ppGpp by an ATP-GTP 3'-pyrophosphotransferase as well as an ability to degrade (p)ppGpp by a Mn(2+)-dependent 3'-pyrophosphohydrolase. Removal of the C-terminal half-protein has reciprocal regulatory effects on the activities of the N-terminal half-protein. Compared to the full-length protein, deletion activates (p)ppGpp synthesis specific activity about 12-fold and simultaneously inhibits (p)ppGpp degradation specific activity about 150-fold to shift the balance of the two activities in favor of synthesis. Cellular (p)ppGpp accumulation behavior is consistent with these changes. The bifunctional N-terminal half-protein can be further dissected into overlapping monofunctional subdomains, since purified peptides display either degradation activity (residues 1 to 224) or synthetic activity (residues 79 to 385) in vitro. These assignments can also apply to RelA and SpoT. The ability of Rel(Seq) to mediate (p)ppGpp accumulation during amino acid starvation in S. equisimilis is absent when the protein is expressed ectopically in Escherichia coli. Fusing the N-terminal half of Rel(Seq) with the C-terminal domain of RelA creates a chimeric protein that restores the stringent response in E. coli by inhibiting unregulated degradation and restoring regulated synthetic activity. Reciprocal intramolecular regulation of the dual activities may be a general intrinsic feature of Rel/Spo homolog proteins.
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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.