A binuclear metallohydrolase model for RelA/SpoT-Homolog (RSH) hydrolases.

When challenged by starvation, bacterial organisms synthesize guanosine pentaphosphate and tetraphosphate, collectively denoted as (p)ppGpp, as second messengers to reprogram metabolism toward slower growth and enhanced stress tolerance. When starvation is alleviated, the RelA-SpoT Homolog (RSH) hydrolases downregulate (p)ppGpp, cleaving the 3'-diphosphate to produce GTP or GDP. Metazoan RSH hydrolases possess phosphatase activity responsible for converting cytoplasmic NADPH to NADH in mammalian cells.

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.

Mechanisms and inhibition of Porcupine-mediated Wnt acylation.

Wnt signalling is essential for regulation of embryonic development and adult tissue homeostasis, and aberrant Wnt signalling is frequently associated with cancers. Wnt signalling requires palmitoleoylation on a hairpin 2 motif by the endoplasmic reticulum-resident membrane-bound O-acyltransferase Porcupine (PORCN). This modification is indispensable for Wnt binding to its receptor Frizzled, which triggers signalling.