ArticleBMC structural biology2013
A structural role for the PHP domain in E. coli DNA polymerase III.
Article in BMC structural biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 60 citations in OpenAlex.
- Diversity and distribution of bacterial DNA polymerases.Nucleic acids research · 2026Article
- The A, B, C, D's of replicative DNA polymerase fidelity: utilizing high-throughput single-molecule sequencing to understand the molecular basis for DNA polymerase accuracy.Nucleic acids research · 2025Article
- A unique inhibitor conformation selectively targets the DNA polymerase PolC of Gram-positive priority pathogens.Nature communications · 2025Article
- PHP-Family Diesterase fromBiochemistry · 2024Article
- Escherichia coli DNA replication: the old model organism still holds many surprises.FEMS microbiology reviews · 2024Review
- Thermophilic PHP Protein Tyrosine Phosphatases (Cap8C and Wzb) from Mesophilic Bacteria.International journal of molecular sciences · 2024Article
- Molecular basis for proofreading by the unique exonuclease domain of Family-D DNA polymerases.Nature communications · 2023Article
- Pre-Steady-State Kinetic Characterization of an Antibiotic-Resistant Mutant of Staphylococcus aureus DNA Polymerase PolC.Antimicrobial agents and chemotherapy · 2023Article
- A splice site mutation in theHorticulture research · 2023Article
- Structure of eukaryotic DNA polymerase δ bound to the PCNA clamp while encircling DNA.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Polymerization and editing modes of a high-fidelity DNA polymerase are linked by a well-defined path.Nature communications · 2020Article
- An array of basic residues is essential for the nucleolytic activity of the PHP domain of bacterial/archaeal PolX DNA polymerases.Scientific reports · 2019Article
- A structural view of bacterial DNA replication.Protein science : a publication of the Protein Society · 2019Review
- High-fidelity DNA replication in Mycobacterium tuberculosis relies on a trinuclear zinc center.Nature communications · 2017Article
- DNA Replication in Mycobacterium tuberculosis.Microbiology spectrum · 2017Review
- Self-correcting mismatches during high-fidelity DNA replication.Nature structural & molecular biology · 2017Article
- The Eukaryotic Replisome Goes Under the Microscope.Current biology : CB · 2016Review
- The β2 clamp in the Mycobacterium tuberculosis DNA polymerase III αβ2ε replicase promotes polymerization and reduces exonuclease activity.Scientific reports · 2016Article
- Escherichia coli DnaE Polymerase Couples Pyrophosphatase Activity to DNA Replication.PloS one · 2016Article
- Adaptation of the autotrophic acetogen Sporomusa ovata to methanol accelerates the conversion of CO2 to organic products.Scientific reports · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundIn addition to the core catalytic machinery, bacterial replicative DNA polymerases contain a Polymerase and Histidinol Phosphatase (PHP) domain whose function is not entirely understood. The PHP domains of some bacterial replicases are active metal-dependent nucleases that may play a role in proofreading. In E. coli DNA polymerase III, however, the PHP domain has lost several metal-coordinating residues and is likely to be catalytically inactive.
resultsGenomic searches show that the loss of metal-coordinating residues in polymerase PHP domains is likely to have coevolved with the presence of a separate proofreading exonuclease that works with the polymerase. Although the E. coli Pol III PHP domain has lost metal-coordinating residues, the structure of the domain has been conserved to a remarkable degree when compared to that of metal-binding PHP domains. This is demonstrated by our ability to restore metal binding with only three point mutations, as confirmed by the metal-bound crystal structure of this mutant determined at 2.9 Å resolution. We also show that Pol III, a large multi-domain protein, unfolds cooperatively and that mutations in the degenerate metal-binding site of the PHP domain decrease the overall stability of Pol III and reduce its activity.
conclusionsWhile the presence of a PHP domain in replicative bacterial polymerases is strictly conserved, its ability to coordinate metals and to perform proofreading exonuclease activity is not, suggesting additional non-enzymatic roles for the domain. Our results show that the PHP domain is a major structural element in Pol III and its integrity modulates both the stability and activity of the polymerase.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.