PDBsum entry 1j54

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protein ligands metals links
Transferase PDB id
Protein chain
174 a.a. *
EDO ×3
_MN ×2
Waters ×225
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Structure of the n-terminal exonuclease domain of the epsilon subunit of e.Coli DNA polymerase iii at ph 5.8
Structure: DNA polymerase iii, epsilon chain. Chain: a. Fragment: n-terminal exonuclease domain (residues 1-186). Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: enterobacteria phage t7. Expression_system_taxid: 10760.
1.70Å     R-factor:   0.201     R-free:   0.234
Authors: S.Hamdan,P.D.Carr,S.E.Brown,D.L.Ollis,N.E.Dixon
Key ref:
S.Hamdan et al. (2002). Structural basis for proofreading during replication of the Escherichia coli chromosome. Structure, 10, 535-546. PubMed id: 11937058 DOI: 10.1016/S0969-2126(02)00738-4
22-Jan-02     Release date:   16-Oct-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P03007  (DPO3E_ECOLI) -  DNA polymerase III subunit epsilon
243 a.a.
174 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - DNA-directed Dna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
Deoxynucleoside triphosphate
Bound ligand (Het Group name = TMP)
matches with 40.00% similarity
+ DNA(n)
= diphosphate
+ DNA(n+1)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     DNA replication   1 term 
  Biochemical function     nucleic acid binding     4 terms  


DOI no: 10.1016/S0969-2126(02)00738-4 Structure 10:535-546 (2002)
PubMed id: 11937058  
Structural basis for proofreading during replication of the Escherichia coli chromosome.
S.Hamdan, P.D.Carr, S.E.Brown, D.L.Ollis, N.E.Dixon.
The epsilon subunit of the Escherichia coli replicative DNA polymerase III is the proofreading 3'-5' exonuclease. Structures of its catalytic N-terminal domain (epsilon186) were determined at two pH values (5.8 and 8.5) at resolutions of 1.7-1.8 A, in complex with two Mn(II) ions and a nucleotide product of its reaction, thymidine 5'-monophosphate. The protein structure is built around a core five-stranded beta sheet that is a common feature of members of the DnaQ superfamily. The structures were identical, except for differences in the way TMP and water molecules are coordinated to the binuclear metal center in the active site. These data are used to develop a mechanism for epsilon and to produce a plausible model of the complex of epsilon186 with DNA.
  Selected figure(s)  
Figure 3.
Figure 3. Structures of the Active Sites of epsilon, Greek 186 and Other Exonuclease Domains(A and B) Low- and high-pH structures, respectively, of the active site of epsilon, Greek 186. The two Mn(II) ions, Mn[A] and Mn[B] are shown (in orange) coordinated to the 5'-phosphate of TMP. The remainder of the TMP molecules are omitted for clarity (but see Figure 4). Coordinated-water molecules are represented by red spheres.(C-E) Comparative structures of the 3'-5' exonuclease active sites of exonuclease I (PDB code 1FXX) [41], DNA polymerase I (1KRP) [51], and bacteriophage T4 DNA polymerase (1NOY) [7]. Structures were aligned as in Figure 2, and diagrams were drawn using RIBBONS [78].
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 535-546) copyright 2002.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21251255 V.M.Isabella, and V.L.Clark (2011).
Deep sequencing-based analysis of the anaerobic stimulon in Neisseria gonorrhoeae.
  BMC Genomics, 12, 51.  
20854710 W.Yang (2011).
Nucleases: diversity of structure, function and mechanism.
  Q Rev Biophys, 44, 1.  
21317904 Y.Y.Hsiao, C.C.Yang, C.L.Lin, J.L.Lin, Y.Duh, and H.S.Yuan (2011).
Structural basis for RNA trimming by RNase T in stable RNA 3'-end maturation.
  Nat Chem Biol, 7, 236-243.
PDB codes: 3ngy 3ngz 3nh0 3nh1 3nh2
20462377 G.Otting (2010).
Protein NMR using paramagnetic ions.
  Annu Rev Biophys, 39, 387-405.  
19119875 G.A.Cisneros, L.Perera, R.M.Schaaper, L.C.Pedersen, R.E.London, L.G.Pedersen, and T.A.Darden (2009).
Reaction mechanism of the epsilon subunit of E. coli DNA polymerase III: insights into active site metal coordination and catalytically significant residues.
  J Am Chem Soc, 131, 1550-1556.  
19276069 M.Horiuchi, K.Takeuchi, N.Noda, N.Muroya, T.Suzuki, T.Nakamura, J.Kawamura-Tsuzuku, K.Takahasi, T.Yamamoto, and F.Inagaki (2009).
Structural Basis for the Antiproliferative Activity of the Tob-hCaf1 Complex.
  J Biol Chem, 284, 13244-13255.
PDB code: 2d5r
19321497 Silva, F.W.Perrino, and T.Hollis (2009).
DNA binding induces active site conformational change in the human TREX2 3'-exonuclease.
  Nucleic Acids Res, 37, 2411-2417.  
18981218 Y.Y.Hsiao, A.Nakagawa, Z.Shi, S.Mitani, D.Xue, and H.S.Yuan (2009).
Crystal structure of CRN-4: implications for domain function in apoptotic DNA degradation.
  Mol Cell Biol, 29, 448-457.
PDB codes: 3cg7 3cm5 3cm6
  18678932 C.J.Jackson, K.S.Hadler, P.D.Carr, A.J.Oakley, S.Yip, G.Schenk, and D.L.Ollis (2008).
Malonate-bound structure of the glycerophosphodiesterase from Enterobacter aerogenes (GpdQ) and characterization of the native Fe2+ metal-ion preference.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 681-685.
PDB codes: 2zo9 2zoa
19032786 D.Zhang, H.Xiong, J.Shan, X.Xia, and V.L.Trudeau (2008).
Functional insight into Maelstrom in the germline piRNA pathway: a unique domain homologous to the DnaQ-H 3'-5' exonuclease, its lineage-specific expansion/loss and evolutionarily active site switch.
  Biol Direct, 3, 48.  
18534978 F.W.Perrino, Silva, S.Harvey, E.E.Pryor, D.W.Cole, and T.Hollis (2008).
Cooperative DNA binding and communication across the dimer interface in the TREX2 3' --> 5'-exonuclease.
  J Biol Chem, 283, 21441-21452.  
18663010 K.Ozawa, S.Jergic, A.Y.Park, N.E.Dixon, and G.Otting (2008).
The proofreading exonuclease subunit epsilon of Escherichia coli DNA polymerase III is tethered to the polymerase subunit alpha via a flexible linker.
  Nucleic Acids Res, 36, 5074-5082.
PDB codes: 4gx8 4gx9
18780819 M.Brucet, J.Querol-Audí, K.Bertlik, J.Lloberas, I.Fita, and A.Celada (2008).
Structural and biochemical studies of TREX1 inhibition by metals. Identification of a new active histidine conserved in DEDDh exonucleases.
  Protein Sci, 17, 2059-2069.
PDB codes: 3b6o 3b6p
18219121 R.D.Busam (2008).
Structure of Escherichia coli exonuclease I in complex with thymidine 5'-monophosphate.
  Acta Crystallogr D Biol Crystallogr, 64, 206-210.
PDB code: 2qxf
17452359 A.T.Jonstrup, K.R.Andersen, L.B.Van, and D.E.Brodersen (2007).
The 1.4-A crystal structure of the S. pombe Pop2p deadenylase subunit unveils the configuration of an active enzyme.
  Nucleic Acids Res, 35, 3153-3164.
PDB code: 2p51
17229737 J.M.Choi, S.Y.Kang, W.J.Bae, K.S.Jin, M.Ree, and Y.Cho (2007).
Probing the roles of active site residues in the 3'-5' exonuclease of the Werner syndrome protein.
  J Biol Chem, 282, 9941-9951.  
17355961 M.Brucet, J.Querol-Audí, M.Serra, X.Ramirez-Espain, K.Bertlik, L.Ruiz, J.Lloberas, M.J.Macias, I.Fita, and A.Celada (2007).
Structure of the dimeric exonuclease TREX1 in complex with DNA displays a proline-rich binding site for WW Domains.
  J Biol Chem, 282, 14547-14557.
PDB codes: 2o4g 2o4i
17910025 M.John, and G.Otting (2007).
Strategies for measurements of pseudocontact shifts in protein NMR spectroscopy.
  Chemphyschem, 8, 2309-2313.  
17096205 M.John, M.J.Headlam, N.E.Dixon, and G.Otting (2007).
Assignment of paramagnetic (15)N-HSQC spectra by heteronuclear exchange spectroscopy.
  J Biomol NMR, 37, 43-51.  
17311884 M.Maiti, H.C.Lee, and Y.Liu (2007).
QIP, a putative exonuclease, interacts with the Neurospora Argonaute protein and facilitates conversion of duplex siRNA into single strands.
  Genes Dev, 21, 590-600.  
17293595 Silva, S.Choudhury, S.L.Bailey, S.Harvey, F.W.Perrino, and T.Hollis (2007).
The crystal structure of TREX1 explains the 3' nucleotide specificity and reveals a polyproline II helix for protein partnering.
  J Biol Chem, 282, 10537-10543.
PDB codes: 2ioc 2oa8
17452361 X.C.Su, S.Jergic, M.A.Keniry, N.E.Dixon, and G.Otting (2007).
Solution structure of Domains IVa and V of the tau subunit of Escherichia coli DNA polymerase III and interaction with the alpha subunit.
  Nucleic Acids Res, 35, 2825-2832.
PDB code: 2aya
17437714 Y.Zuo, H.Zheng, Y.Wang, M.Chruszcz, M.Cymborowski, T.Skarina, A.Savchenko, A.Malhotra, and W.Minor (2007).
Crystal structure of RNase T, an exoribonuclease involved in tRNA maturation and end turnover.
  Structure, 15, 417-428.
PDB codes: 2f96 2is3
16885451 A.K.Chikova, and R.M.Schaaper (2006).
Mutator and antimutator effects of the bacteriophage P1 hot gene product.
  J Bacteriol, 188, 5831-5838.  
16517598 A.Wieczorek, and C.S.McHenry (2006).
The NH2-terminal php domain of the alpha subunit of the Escherichia coli replicase binds the epsilon proofreading subunit.
  J Biol Chem, 281, 12561-12567.  
16767502 C.Schmitz, M.John, A.Y.Park, N.E.Dixon, G.Otting, G.Pintacuda, and T.Huber (2006).
Efficient chi-tensor determination and NH assignment of paramagnetic proteins.
  J Biomol NMR, 35, 79-87.  
16608433 J.L.Beck, T.Urathamakul, S.J.Watt, M.M.Sheil, P.M.Schaeffer, and N.E.Dixon (2006).
Proteomic dissection of DNA polymerization.
  Expert Rev Proteomics, 3, 197-211.  
17135487 J.M.Kupsco, M.J.Wu, W.F.Marzluff, R.Thapar, and R.J.Duronio (2006).
Genetic and biochemical characterization of Drosophila Snipper: A promiscuous member of the metazoan 3'hExo/ERI-1 family of 3' to 5' exonucleases.
  RNA, 12, 2103-2117.  
17029243 K.H.Chin, C.Y.Yang, C.C.Chou, A.H.Wang, and S.H.Chou (2006).
The crystal structure of XC847 from Xanthomonas campestris: a 3'-5' oligoribonuclease of DnaQ fold family with a novel opposingly shifted helix.
  Proteins, 65, 1036-1040.
PDB code: 2gbz
16740953 M.A.Keniry, A.Y.Park, E.A.Owen, S.M.Hamdan, G.Pintacuda, G.Otting, and N.E.Dixon (2006).
Structure of the theta subunit of Escherichia coli DNA polymerase III in complex with the epsilon subunit.
  J Bacteriol, 188, 4464-4473.
PDB code: 2axd
16973612 T.W.Kirby, S.Harvey, E.F.DeRose, S.Chalov, A.K.Chikova, F.W.Perrino, R.M.Schaaper, R.E.London, and L.C.Pedersen (2006).
Structure of the Escherichia coli DNA polymerase III epsilon-HOT proofreading complex.
  J Biol Chem, 281, 38466-38471.
PDB code: 2ido
15952889 A.Johnson, and M.O'Donnell (2005).
Cellular DNA replicases: components and dynamics at the replication fork.
  Annu Rev Biochem, 74, 283-315.  
16077097 A.K.Chikova, and R.M.Schaaper (2005).
The bacteriophage P1 hot gene product can substitute for the Escherichia coli DNA polymerase III {theta} subunit.
  J Bacteriol, 187, 5528-5536.  
15661738 F.W.Perrino, S.Harvey, S.McMillin, and T.Hollis (2005).
The human TREX2 3' -> 5'-exonuclease structure suggests a mechanism for efficient nonprocessive DNA catalysis.
  J Biol Chem, 280, 15212-15218.
PDB code: 1y97
16281054 M.Wu, M.Reuter, H.Lilie, Y.Liu, E.Wahle, and H.Song (2005).
Structural insight into poly(A) binding and catalytic mechanism of human PARN.
  EMBO J, 24, 4082-4093.
PDB codes: 2a1r 2a1s
15576035 E.F.Derose, T.W.Kirby, G.A.Mueller, A.K.Chikova, R.M.Schaaper, and R.E.London (2004).
Phage like it HOT: solution structure of the bacteriophage P1-encoded HOT protein, a homolog of the theta subunit of E. coli DNA polymerase III.
  Structure, 12, 2221-2231.
PDB code: 1se7
15459336 R.Gupta, S.M.Hamdan, N.E.Dixon, M.M.Sheil, and J.L.Beck (2004).
Application of electrospray ionization mass spectrometry to study the hydrophobic interaction between the epsilon and theta subunits of DNA polymerase III.
  Protein Sci, 13, 2878-2887.  
15090519 S.A.Taft-Benz, and R.M.Schaaper (2004).
The theta subunit of Escherichia coli DNA polymerase III: a role in stabilizing the epsilon proofreading subunit.
  J Bacteriol, 186, 2774-2780.  
15039570 T.J.Fiedler, H.A.Vincent, Y.Zuo, O.Gavrialov, and A.Malhotra (2004).
Purification and crystallization of Escherichia coli oligoribonuclease.
  Acta Crystallogr D Biol Crystallogr, 60, 736-739.  
14704353 Y.Shen, X.F.Tang, H.Yokoyama, E.Matsui, and I.Matsui (2004).
A 21-amino acid peptide from the cysteine cluster II of the family D DNA polymerase from Pyrococcus horikoshii stimulates its nuclease activity which is Mre11-like and prefers manganese ion as the cofactor.
  Nucleic Acids Res, 32, 158-168.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.