In eubacteria ppGpp (guanosine 3'-diphosphate 5'-diphosphate) is a mediator of the stringent response that coordinates a variety of cellular activities in response to changes in nutritional abundance. This enzyme catalyzes both the formation of pppGpp, which is then hydrolyzed to form ppGpp, as well as the hydrolysis of ppGpp. RelA is probably a key factor in the pathogenesis of M.tuberculosis as it regulates the intracellular concentrations of (p)ppGpp. guanosine 3',5'-bis(diphosphate) + H2O = diphosphate + GDP + H(+) ATP + GTP = AMP + guanosine 3'-diphosphate 5'-triphosphate Binds 1 Mg(2+) ion per subunit. Binds 1 Mn(2+) ion per subunit. Transferase activity occurs when RelA binds to a complex containing uncharged tRNA, ribosomes, and mRNA (RelA activating complex or RAC). The addition of charged tRNA to this complex has the opposite effect, inhibiting transferase activity and activating hydrolysis activity. Purine metabolism; ppGpp biosynthesis; ppGpp from GDP: step 1/1. Purine metabolism; ppGpp biosynthesis; ppGpp from GTP: step 1/2. Homotrimer. By MazG. Based on a mutagenesis study of the catalytic fragment (residues 1-394), the (p)ppGpp phosphohydrolase domain seems to encompass approximately the first 203 residues, while the (p)ppGpp synthase domain seems to be found between residues 87 and 394. Cells lacking this gene fail to synthesize ppGpp in response to starvation. Belongs to the RelA/SpoT family. Extended N-terminus.