Guanosine-3’,5’-bis(diphosphate)-pyrophosphohydrolase MESH1(HDDC3) contains an active site for ppGpp hydrolysis and a conserved His-Asp-box motif for Mn(2+) binding. In accordance with its structure, HDDC3 effectively catalyzes the hydrolysis of guanosine 3’,5’-diphosphate(ppGpp) both in vitro and in vivo. In addition, HDDC3 suppresses SpoT-deficient lethality and RelA-induced delayed cell growth in bacteria.