Structural Analysis of (p)ppGpp Reveals Its Versatile Binding Pattern for Diverse Types of Target Proteins

Kushwaha, G.S.; Patra, Anupam; Bhavesh, Neel Sarovar

doi:10.3389/fmicb.2020.575041

Cited by 3 publications

(2 citation statements)

References 79 publications

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“…Accordingly, aligning 26 (p)ppGpp molecules by their guanine ring and ribose reveals a veritable tree-like diversity in the conformations of the phosphate arms (Figure 4c). These observations were recently supported by molecular dynamics analyses, which suggested that the two linear arms of (p)ppGpp make it much more flexible than other signaling nucleotides (50). (p)ppGpp's ability to interact with a diversity of proteins in such diverse conformations tells us that there is likely much more to learn about its breadth of interaction partners.…”

Section: (P)ppgpp Adopts Flexible Conformations In Binding Diverse Po...mentioning

confidence: 91%

Regulatory Themes and Variations by the Stress-Signaling Nucleotide Alarmones (p)ppGpp in Bacteria

2021

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Bacterial stress-signaling alarmones are important components of a protective network against diverse stresses such as nutrient starvation and antibiotic assault. pppGpp and ppGpp, collectively (p)ppGpp, have well-documented regulatory roles in gene expression and protein translation. Recent work has highlighted another key function of (p)ppGpp: inducing rapid and coordinated changes in cellular metabolism by regulating enzymatic activities, especially those involved in purine nucleotide synthesis. Failure of metabolic regulation by (p)ppGpp results in the loss of coordination between metabolic and macromolecular processes, leading to cellular toxicity. In this review, we document how (p)ppGpp and newly characterized nucleotides pGpp and (p)ppApp directly regulate these enzymatic targets for metabolic remodeling. We examine targets’ common determinants for alarmone interaction as well as their evolutionary diversification. We highlight classical and emerging themes in nucleotide signaling, including oligomerization and allostery along with metabolic interconversion and crosstalk, illustrating how they allow optimized bacterial adaptation to their environmental niches.

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Section: (P)ppgpp Adopts Flexible Conformations In Binding Diverse Po...mentioning

confidence: 91%

Regulatory Themes and Variations by the Stress-Signaling Nucleotide Alarmones (p)ppGpp in Bacteria

2021

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“…Collectively, these changes result in a slowdown of cell growth [Pacios et al, 2020]. The set of identified targets affected by (p)ppGpp continues to expand [Kushwaha et al, 2020]. For instance, the interaction of (p)ppGpp with the translation initiation factor IF2 halts protein synthesis [Diez et al, 2020], the suppression of GTPase activity by (p)ppGpp leads to a reduction in the number of mature ribosomes [Corrigan et al, 2016], and (p)ppGpp interaction with HPRT inhibits purine metabolism [Anderson et al, 2019].…”

Section: (P)ppgpp Alarmonesmentioning

confidence: 99%

Alarmones as bacterial persistence factor

Sidorov,

Tkachenko

2023

Bulletin of Perm University. Biology

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The treatment of bacterial infections with antibiotics is significantly complicated because of the adaptive mechanisms employed by bacteria. Chronic and recurrent infections are often linked to bacterial persis-tence, biofilm formation, and antibiotic tolerance. These processes result in reduced metabolic activity, rendering bacteria insensitive to conventional antibiotics that primarily target actively growing cells. The stringent re-sponse, regulated by (p)ppGpp alarmone molecules, serves as a stress adaptation mechanism. It is conserved across numerous bacterial species and plays an important role in long-term survival under nutrient-depleted con-ditions. (p)ppGpp alarmones also play a significant role in bacterial persistence and the formation of biofilms. The pursuit of novel antibacterial agents that specifically target (p)ppGpp synthesis, thereby inhibiting the strin-gent response, presents a promising strategy in the battle against bacterial infections. In this context, alarmone synthetase inhibitors emerge as promising candidates for clinical application, as they have demonstrated their effectiveness in suppressing bacterial survival mechanisms, inhibiting biofilm formation, and reducing antibiotic tolerance and bacterial persistence.

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Guanosine tetraphosphate (ppGpp) is a new player in Brassica napus L. seed development

Turkan,

Kulasek,

Zienkiewicz

et al. 2024

Food Chemistry

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Structural Analysis of (p)ppGpp Reveals Its Versatile Binding Pattern for Diverse Types of Target Proteins

Cited by 3 publications

References 79 publications

Regulatory Themes and Variations by the Stress-Signaling Nucleotide Alarmones (p)ppGpp in Bacteria

Regulatory Themes and Variations by the Stress-Signaling Nucleotide Alarmones (p)ppGpp in Bacteria

Alarmones as bacterial persistence factor

Guanosine tetraphosphate (ppGpp) is a new player in Brassica napus L. seed development

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