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Life Sciences

Chemistry & Biochemistry Faculty Publications

Alarmone

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Full-Text Articles in Physical Sciences and Mathematics

Sound The (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide Pgpp, Areej Malik, Megan A. Hept, Erin B. Purcell Jan 2023

Sound The (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide Pgpp, Areej Malik, Megan A. Hept, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

It has recently become evident that the bacterial stringent response is regulated by a triphosphate alarmone (pGpp) as well as the canonical tetra- and pentaphosphate alarmones ppGpp and pppGpp [together, (p)ppGpp]. Often dismissed in the past as an artifact or degradation product, pGpp has been confirmed as a deliberate endpoint of multiple synthetic pathways utilizing GMP, (p)ppGpp, or GDP/GTP as precursors. Some early studies concluded that pGpp functionally mimics (p)ppGpp and that its biological role is to make alarmone metabolism less dependent on the guanine energy charge of the cell by allowing GMP-dependent synthesis to continue when GDP/GTP has been …


Unique Features Of Alarmone Metabolism In Clostridioides Difficile, Asia Poudel, Astha Pokhrel, Adenrele Oludiran, Estevan J. Coronado, Kwincy Alleyne, Marrett M. Gilfus, Raj K. Gurung, Surya B. Adhikari, Erin B. Purcell Jan 2022

Unique Features Of Alarmone Metabolism In Clostridioides Difficile, Asia Poudel, Astha Pokhrel, Adenrele Oludiran, Estevan J. Coronado, Kwincy Alleyne, Marrett M. Gilfus, Raj K. Gurung, Surya B. Adhikari, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The “magic spot” alarmones (pp)pGpp, previously implicated in Clostridioides difficile antibiotic survival, are synthesized by the RelA-SpoT homolog (RSH) of C. difficile (RSHCd) and RelQCd. These enzymes are transcriptionally activated by diverse environmental stresses. RSHCd has previously been reported to synthesize ppGpp, but in this study, we found that both clostridial enzymes exclusively synthesize pGpp. While direct synthesis of pGpp from a GMP substrate, and (p)ppGpp hydrolysis into pGpp by NUDIX hydrolases, have previously been reported, there is no precedent for a bacterium synthesizing pGpp exclusively. Hydrolysis of the 5′ phosphate or pyrophosphate from GDP …