This entry includes bifunctional polynucleotide phosphatase/kinase PNKP from animals. PNKP plays a key role in the repair of DNA damage, functioning as part of both the non-homologous end-joining (NHEJ) and base excision repair (BER) pathways. It has been shown that the DNA 3'-phosphatase activity of PNKP takes precedence over its DNA 5'-kinase activity in vitro []. It contains a forkhead-associated domain, which is a protein-protein interaction domain required for the association of PNKP with CK2-phosphorylated XRCC1 and XRCC4, and independent DNA 3'-phosphatase and 5'-kinase domains [].
This entry represents the C-terminal domain of the bifunctional enzyme T4 polynucleotide kinase/phosphatase, PNKP (also known as PseT). The PNKP phosphatase domain can catalyse the hydrolytic removal of the 3'-phosphoryl of DNA, RNA and deoxynucleoside 3'-monophosphates [].
This entry represents the ligase domain found in the PNKP (polynucleotide kinase-phosphatase) protein, which is a classical ligase nucleotidyltransferase module of bacteria. PNKP is the end-healing and end-sealing component of an RNA-repair system present in diverse bacteria from ten different phyla. RNA breakage by site-specific 'ribotoxins' is an ancient mechanism by which microbes respond to cellular stress and distinguish self from non-self. Ribotoxins are trans-esterifying endonucleases that generate 5'-OH and 2',3' cyclic phosphate termini. Repair of this type of RNA damage is feasible via sequential enzymatic end-healing and end-sealing steps [].
Members of this family are the bacterial polynucleotide kinase-phosphatase (Pnkp) enzymes that prepare broken RNA termini for sealing by RNA ligase []. Their genes co-occur with genes for the 3' terminal RNA ribose 2'-O-methyltransferase Hen1, and the pair are thought to form a bacterial RNA repair cassette, where a combination of Pnkp (RNA repair) and Hen1 (RNA modification) serves to first repair RNA damage from ribotoxins and then perform a modification that prevents the damage from recurring [].
This entry represents the metallophosphatase domain of Bacillus subtilis PrpE and related proteins. PrpE (protein phosphatase E) is a bacterial member of the PPP (phosphoprotein phosphatase) family of serine/threonine phosphatases and a key signal transduction pathway component controlling the expression of spore germination receptors GerA and GerK in Bacillus subtilis. PrpE is closely related to ApaH (also known symmetrical Ap(4)A hydrolase and bis(5'nucleosyl)-tetraphosphatase). PrpE has specificity for phosphotyrosine only, unlike the serine/threonine phosphatases to which it is related []. The Bacilli members of this family are single domain proteins while the other members have N- and C-terminal domains in addition to this phosphatase domain. Polynucleotide kinase/phosphatase (Pnkp) is the end-healing and end-sealing component of an RNA repair system present in bacteria []. It is composed of three catalytic modules: an N-terminal polynucleotide 5' kinase, a central 2',3' phosphatase, and a C-terminal ligase. Pnkp is a Mn(2+)-dependent phosphodiesterase-monoesterase that dephosphorylates 2',3'-cyclic phosphate RNA ends. An RNA binding site is suggested by a continuous tract of positive surface potential flanking the active site [].The PPP (phosphoprotein phosphatase) family, to which PrpE belongs, is one of two known protein phosphatase families specific for serine and threonine. The PPP family also includes: PP1, PP2A, PP2B (calcineurin), PP4, PP5, PP6, PP7, Bsu1, RdgC, PrpA/PrpB, and ApA4 hydrolase. The PPP catalytic domain is defined by three conserved motifs (-GDXHG-, -GDXVDRG- and -GNHE-). The PPP enzyme family is ancient with members found in all eukaryotes, and in most bacterial and archeal genomes. Dephosphorylation of phosphoserines and phosphothreonines on target proteins plays a central role in the regulation of many cellular processes [, ]. PPPs belong to the metallophosphatase (MPP) superfamily.
