Nucleotidyltransferase (NT) domain of RelA- and SpoT-like ppGpp synthetases and hydrolases.
This family includes the catalytic domains of Escherichia coli ppGpp synthetase (RelA), ppGpp synthetase/hydrolase (SpoT), and related proteins. RelA synthesizes (p)ppGpp in response to amino-acid starvation and in association with ribosomes. (p)ppGpp triggers the bacterial stringent response. SpoT catalyzes (p)ppGpp synthesis under carbon limitation in a ribosome-independent manner. It also catalyzes (p)ppGpp degradation. Gram-negative bacteria have two enzymes involved in (p)ppGpp metabolism while most Gram-positive organisms have a single Rel-Spo enzyme (Rel), which both synthesizes and degrades (p)ppGpp. The Arabidopsis thaliana Rel-Spo proteins, At-RSH1,-2, and-3 appear to regulate a rapid (p)ppGpp-mediated response to pathogens and other stresses. This catalytic domain is found in association with an N-terminal HD domain and a C-terminal metal dependent phosphohydrolase domain (TGS). Some Rel-Spo proteins also have a C-terminal regulatory ACT domain. This subgroup belongs to the Pol beta-like NT superfamily. In the majority of enzymes in this superfamily, two carboxylates, Dx[D/E], together with a third more distal carboxylate, coordinate two divalent metal cations involved in a two-metal ion mechanism of nucleotide addition.Two of the three catalytic carboxylates are found in Rel-Spo enzymes, with the second carboxylate of the DXD motif missing. Evidence supports a single-cation synthetase mechanism.
Comment:For Streptococcus equisimilis SeqRel, a reciprocal regulatory mechanism ensures that the opposing activities, (p)ppGpp synthesis and degradation, located in two domains within the same monomer, are not co-induced.
Structure:1VJ7_A, Streptococcus equisimilis, bifunctional catalytic fragment of Relseq monomer, showing the synthetase active site bound with GDP, (hydrolase-OFF/synthetase-ON), contacts determined at 4A. - View structure with Cn3D
Comment:The VJ7 structure contains two monomers, one in the hydrolase-OFF/synthetase-ON state, the other in the hydrolase-ON/synthetase-OFF state.
Jiyao W et al.(2023). "The conserved domain database in 2023.",