nucleotide-binding domain (NBD) of the exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GppA) domain family
Members of the PPX/GppA family are involved in bacterial survival and metabolism. They may play distinct biochemical roles involved in polyphosphate and (p)ppGpp metabolic pathways. Guanosine pentaphosphate (pppGpp) phosphohydrolase (GppA; EC 3.6.1.40) plays a key role in (p)ppGpp homeostasis. It specifically catalyzes the conversion of pppGpp to ppGpp (guanosine tetraphosphate). Sharing a similar domain structure, GppA is indistinguishable from exopolyphosphatase (PPX; EC 3.6.1.11), which mediates the metabolism of cellular inorganic polyphosphate. Especially, it is responsible for the maintenance of appropriate levels of cellular inorganic polyphosphate (PolyP). Some bacteria, such as Escherichia coli, possesses two homologs, EcGppA and EcPPX. Some others, such as Helicobacter pylori and Aquifex aeolicus, encode only one PPX/GppA homolog, which may play important roles in the homeostasis of both (p)ppGpp and PolyP. The PPX/GppA family belongs to the ASKHA (Acetate and Sugar Kinases/Hsc70/Actin) superfamily of phosphotransferases, all members of which share a common characteristic five-stranded beta sheet occurring in both the N- and C-terminal domains.