This domain is associated with the N terminus of members of the PHP superfamily, this includes:
subunit of bacterial DNA polymerase III,
eukaryotic DNA polymerase,
X-family of DNA polymerases,
histidinol phosphatases,
and a number of uncharacterised protein families.
In common for all PHP proteins is the presence of four conserved sequence motifs that contain invariant histidine and aspartate residues implicated in metal ion coordination. As part of DNA polymerases, the PHP domain was suggested to hydrolyse pyrophosphate and thereby shift the reaction equilibrium toward nucleotide polymerisation. However, it cannot be ruled out that the PHP domain possesses a nuclease activity, particularly in the repair polymerases of the X-family. No functional information is available for standalone proteins that belong to the PHP superfamily.
The crystal structure of the YcdX protein from Escherichia coli has been determined to 1.6-A resolution. YcdX has an unusual topology of a alpha 7_beta 7 barrel compared with the more common alpha 8_beta 8 (TIM) barrel. The C-terminal helix caps the barrel on the N-terminal side. The deep cleft at the C-terminal side of the barrel contains the three zinc binding residues. These residues are invariant in the YcdX family confirming their functional importance.
Only four proteins with known structures have a similar trinuclear zinc catalytic site. All four (nuclease P1, endonuclease IV, alkaline phosphatase, and phospholipase C) hydrolyse the phosphoester bond. This finding suggests a similar activity for YcdX. YcdX is among the genes significantly induced in response to the DNA damage, therefore indicating that members of the YcdX family may be involved in DNA repair [(PUBMED:12661000)].
Phosphoesterase domains associated with DNA polymerases of diverse origins.
Nucleic Acids Res. 1998; 26: 3746-52
Display abstract
Computer analysis of DNA polymerase protein sequences revealed previously unidentified conserved domains that belong to two distinct superfamilies of phosphoesterases. The alpha subunits of bacterial DNA polymerase III and two distinct family X DNA polymerases are shown to contain an N-terminal domain that defines a novel enzymatic superfamily, designated PHP, after polymerase and histidinol phosphatase. The predicted catalytic site of the PHP superfamily consists of four motifs containing conserved histidine residues that are likely to be involved in metal-dependent catalysis of phosphoester bond hydrolysis. The PHP domain is highly conserved in all bacterial polymerase III alpha subunits, but in proteobacteria and mycoplasmas, the conserved motifs are distorted, suggesting a loss of the enzymatic activity. Another conserved domain, found in the small subunits of archaeal DNA polymerase II and eukaryotic DNA polymerases alpha and delta, is shown to belong to the superfamily of calcineurin-like phospho-esterases, which unites a variety of phosphatases and nucleases. The conserved motifs required for phospho-esterase activity are intact in the archaeal DNA polymerase subunits, but are disrupted in their eukaryotic orthologs. A hypothesis is proposed that bacterial and archaeal replicative DNA polymerases possess intrinsic phosphatase activity that hydrolyzes the pyrophosphate released during nucleotide polymerization. As proposed previously, pyrophosphate hydrolysis may be necessary to drive the polymerization reaction forward. The phosphoesterase domains with disrupted catalytic motifs may assume an allosteric, regulatory function and/or bind other subunits of DNA polymerase holoenzymes. In these cases, the pyrophosphate may be hydrolyzed by a stand-alone phosphatase, and candidates for such a role were identified among bacterial PHP superfamily members.
Metabolism (metabolic pathways involving proteins which contain this domain)
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This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with POLIIIAc domain which could be assigned to a KEGG orthologous group, and not all proteins containing POLIIIAc domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
Crystal structure of two-domain protein containing predicted php-like metal-dependent phosphoesterase (yp_001300751.1) from bacteroides vulgatus atcc 8482 at 2.20 a resolution
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