Reciprocal growth control by competitive binding of nucleotide second messengers to a metabolic switch in Caulobacter crescentus

Diurnal metabolic control in cyanobacteria requires perception of second messenger signaling molecule c-di-AMP by the carbon control protein SbtB

“…Cross-talk between second messenger nucleotides is perhaps a more common phenomenon than so far realized. Recently, it was found that the second messengers c-di-GMP and (p)ppGpp reciprocally control Caulobacter crescentus growth by competitive binding to a metabolic switch protein, SmbA ( 38 ). With this in mind, SbtB might play a similar role in cyanobacterial physiology.…”

Photoaffinity capture compounds to profile the Magic Spot Nucleotide interactomes

“…Interestingly, transcriptional control of the zwf operon by MSN was already observed by Shyp et al in 2021 in C. crescentus . [17] A subset of unique targets, despite a high overlap of pGpp with (p)ppGp regarding interactors also has recently been found by Wang using DRaCALA in Bacillus. [22] The differentiation of MSN targets with regards to the degree of phosphorylation is underlined even more in the case of pppGpp-CC (59 hits), which enriched more than 35 % of proteins not captured by ppGpp-CCs or pGpp-CC (Figure 3, A, right).…”

“…Bookmark not defined .,15] Through these direct interactions, (pp)pGpp modulates bacterial DNA replication, ribosome biogenesis and hibernation, translation, metabolism, and pathogenicity. [16,17] In Mycobacterium tuberculosis ( Mtb ), it has recently been demonstrated that inhibition of Rel Mtb -the enzyme responsible for MSN production-can directly kill nutrient starved Mtb and further enhances the killing potency of the known Mtb drug isoniazid in a mouse model. This highlights the importance to increase understanding of MSN function.…”

Photoaffinity Capture Compounds to Profile the Magic Spot Nucleotide Interactomes**

“…[32] In this particular case, we used these intermediates in a Cucatalyzed 1,3-dipolar cycloaddition reaction with amino-PEG 3 -azide. The corresponding triazole-containing click products (17)(18)(19)(20) represent a family of phosphate modified amino-MSN and were isolated in yields of 36-81 %. The amino functionality now enabled ready modification with commercially available NHS esters, such as e.g., photoaffinity labeled and biotinylated linkers (Scheme 2).…”

“…[5,15] Through these direct interactions, (p)ppGpp modulates bacterial DNA replication, ribosome biogenesis and hibernation, translation, metabolism, and pathogenicity. [16,17] In Mycobacterium tuberculosis (Mtb), it has recently been demonstrated that inhibition of Rel Mtbthe enzyme responsible for MSN production-can directly kill nutrient starved Mtb and further enhances the killing potency of the known Mtb drug isoniazid in a mouse model. This highlights the importance to increase understanding of MSN function.…”