HDDC3, also known as guanosine-3',5'-bis(diphosphate)-pyrophosphohydrolase MESH1, contains an active site for ppGpp hydrolysis and a conserved His-Asp-box motif for Mn(2+) binding. Consistent with these structural data, HDDC3 efficiently catalyzes hydrolysis of guanosine 3',5'-diphosphate (ppGpp) both in vitro and in vivo. HDDC3 also suppresses SpoT-deficient lethality and RelA-induced delayed cell growth in bacteria. Recombinant human HDDC3 protein, fused to His-tag at N-terminus, was expressed in E.coli and purified by using conventional chromatography.