PROSITE documentation PDOC52099

Polyphosphate kinase family-1 (PPK1) C-terminal 1 (C1) and 2 (C2) domains profiles

Inorganic polyphosphate (polyP) is an ancient and evolutionarily conserved biopolymer consisting of phosphate monomers linked together via high-energy phosphoanhydride bonds. PolyP chains can range in length from three to over one thousand inorganic phosphate (Pi) residues. Inorganic polyP has been present since pre-biotic times and has been proposed as an energy distributor in a pre-ATP world. PolyP has been found to be present in organisms that represent species from each domain in nature: archaebacteria, bacteria, protista, fungi, plantae and animalia. PolyP represents a reservoir of phosphorous and apparently is also involved in various forms of stress resistance such as tolerance against heavy metals, elevated temperature, or reactive oxygen species and can fulfill functions in virulence, motility, biofilm formation, and cell cycle control. It can be formed either abiotically (vulcanism) or biologically by the action of polyP kinases (PPKs in prokaryotes) or other enzymes (in eukaryotes). PPKs are key enzymes that are connected to the metabolism of polyP. These enzymes catalyse the polymerisation and degradation of the linear polyP chain. In prokaryotes, two types of PPKs are known to catalyze the reversible formation of polyP from ATP: PPK1 and PPK2 (see <PDOC52101>). PPK1 and PPK2 homologues have been found only in one higher member of Eucarya, Dictyostelium discoideum, which most likely obtained it by horizontal gene transfer from Bacteria. PPK1 and PPK2 are separate entities with distinct enzymology, they do not shares significant sequence identity and adopt distinct structural folds. While both enzyme families are capable of catalyzing polyP synthesis, PPK1s preferentially synthesize polyP from nucleoside triphosphates, and PPK2s preferentially consume polyP to phosphorylate nucleoside mono- or diphosphates. PPK1 type PPKs consist of an N-terminal (N) domain, a head (H) domain, and two closely related carboxy-terminal domains (C1 and C2) [1,2,3,4,5].

The C1 and C2 domains are highly conserved in the PPK1 family. Both the C1 and C2 domains consist of a seven-stranded mixed β-sheet flanked by five α-helices (see <PDB:1XDO>). However, the structural topology and relative orientations of the helices to the β-sheet in these two domains are different. Some of the residues crucial for the enzyme catalytic activity are located in these two domains. The first step of PPK1-catalysed polyP synthesis involves the autophosphorylation of a histidine residues, and PPK1 is therefore a histidine kinase. There is no structural similarity between PPK1 and other histidine kinases. However, in spite of the lack of sequence homology, the C1 and C2 domains of PPK1, a protein histidine kinase, are structurally similar to the catalytic domain of phospholipase D (PLD) (see <PDOC50035>), a lipid phosphatase. It should be noted that, whereas the first step of the PPK1 reaction is autophosphorylation of a histidine residue, the first step of the PLD reaction is the transfer of a phosphate moiety to a PLD histidine residue. PLD also contains two repetitive catalytic domains, and each PLD domain consists of an eight-stranded mixed β-sheet flanked by five α-helices, with a topological arrangement different from that of PPK. Some residues in the active-site motif H-x-K-x(4)-D-x(6)-G-S-x-N of the PLD superfamily are spatially conserved in the active site of PPK. It is possible that PPK and the PLD family have a common ancestor and diverged early in evolution. It has been proposed that a PPK C1 histidine functions as a nucleophile attacking the phosphodiester bond of the γ-phosphate group of ATP, whereas a PPK C2 histidine functions as a general acid protonating the oxygen atom between the β- and γ-phosphate [1].

The profiles we developed cover respectively the entire PPK1 C1 and C2 domains.