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A conserved alarmone as a direct regulator of purine metabolism

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The conserved nucleotide diadenosine tetraphosphate (Ap4A) is induced under various stresses, including heat. In a non-biased screen, we identified a critical role of Ap4A in inhibiting a central step in purine metabolism and heat resistance. We clarify the molecular mechanism of Ap4A action on the inosine-5′-monophosphate dehydrogenase (IMPDH) enzyme, showing Ap4A as a bona fide nucleotide second messenger.

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Fig. 1: Ap4A regulates IMPDH.

References

  1. Lee, P. C., Bochner, B. R. & Ames, B. N. AppppA, heat-shock stress, and cell oxidation. Proc. Natl Acad. Sci. USA 80, 7496–7500 (1983). A classic review article describing the early discovery of Ap4A as a potential alarmone.

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This is a summary of: Giammarinaro, P. I. et al. Diadenosine tetraphosphate regulates biosynthesis of GTP in Bacillus subtilis. Nat. Microbiol. https://doi.org/10.1038/s41564-022-01193-x (2022).

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A conserved alarmone as a direct regulator of purine metabolism. Nat Microbiol 7, 1331–1332 (2022). https://doi.org/10.1038/s41564-022-01194-w

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