Synthetase and Hydrolase Specificity Collectively Excludes 2'-Deoxyguanosine from Bacterial Alarmone.

In response to starvation, virtually all bacteria pyrophosphorylate the 3'-hydroxy group of GTP or GDP to produce two messenger nucleotides collectively denoted as (p)ppGpp. Also known as alarmones, (p)ppGpp reprograms bacterial physiology to arrest growth and promote survival. Intriguingly, although cellular concentration of dGTP is two orders of magnitude lower than that of GTP, alarmone synthetases are highly selective against using 2'-deoxyguanosine (2dG) nucleotides as substrates.

Identification of a broadly conserved family of enzymes that hydrolyze (p)ppApp.

Bacteria produce a variety of nucleotide second messengers to adapt to their surroundings. Although chemically similar, the nucleotides guanosine penta- and tetraphosphate [(p)ppGpp] and adenosine penta- and tetraphosphate [(p)ppApp] have distinct functions in bacteria. (p)ppGpp mediates survival under nutrient-limiting conditions and its intracellular levels are regulated by synthetases and hydrolases belonging to the RelA-SpoT homolog (RSH) family of enzymes.