ArticleJournal of molecular biology2020
Molecular Mechanism of Regulation of the Purine Salvage Enzyme XPRT by the Alarmones pppGpp, ppGpp, and pGpp.
Article in Journal of molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- The alarmone pGpp inhibits translation through GTP depletion.Nucleic acids research · 2026Article
- De novo or Salvage? Nucleotide Availability as a Driver of Bacterial Adaptation and Virulence.MicrobiologyOpen · 2026Review
- 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
- The Emerging Role of (p)ppGpp in DNA Repair and Associated Bacterial Survival against Fluoroquinolones.Gene expression · 2025Article
- Environmental purines decrease Pseudomonas aeruginosa biofilm formation by disrupting c-di-GMP metabolism.Cell reports · 2024Article
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- Termination factor Rho mediates transcriptional reprogramming of Bacillus subtilis stationary phase.PLoS genetics · 2023Article
- 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
- (p)ppGpp - an important player during heat shock response.microLife · 2023Review
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- Crosstalk between guanosine nucleotides regulates cellular heterogeneity in protein synthesis during nutrient limitation.PLoS genetics · 2022Article
- Awakening sleeper cells: a narrative review on bacterial magic spot synthetases as potential drug targets to overcome persistence.Current genetics · 2022Review
- 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
- Regulatory Themes and Variations by the Stress-Signaling Nucleotide Alarmones (p)ppGpp in Bacteria.Annual review of genetics · 2021Review
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- Mutations in a Membrane Permease orAntimicrobial agents and chemotherapy · 2021Article
- Emerging and divergent roles of pyrophosphorylated nucleotides in bacterial physiology and pathogenesis.PLoS pathogens · 2021Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The alarmones pppGpp and ppGpp mediate starvation response and maintain purine homeostasis to protect bacteria. In the bacterial phyla Firmicutes and Bacteroidetes, xanthine phosphoribosyltransferase (XPRT) is a purine salvage enzyme that produces the nucleotide XMP from PRPP and xanthine. Combining structural, biochemical, and genetic analyses, we show that pppGpp and ppGpp, as well as a third newly identified alarmone pGpp, all directly interact with XPRT from the Gram-positive bacterium Bacillus subtilis and inhibit XPRT activity by competing with its substrate PRPP. Structural analysis reveals that ppGpp binds the PRPP binding motif within the XPRT active site. This motif is present in another (p)ppGpp target, the purine salvage enzyme HPRT, suggesting evolutionary conservation in different enzymes. However, XPRT oligomeric interaction is distinct from HPRT in that XPRT forms a symmetric dimer with two (p)ppGpp binding sites at the dimer interface. (p)ppGpp's interaction with an XPRT bridging loop across the interface results in XPRT cooperatively binding (p)ppGpp. Also, XPRT displays differential regulation by the alarmones as it is potently inhibited by both ppGpp and pGpp, but only modestly by pppGpp. Lastly, we demonstrate that the alarmones are necessary for protecting GTP homeostasis against excess environmental xanthine in B. subtilis, suggesting that regulation of XPRT is key for regulating the purine salvage pathway.
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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.