PDBsum entry 2hqa

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protein ligands links
Transferase PDB id
Protein chain
910 a.a. *
PO4 ×3
Waters ×104
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of the catalytic alpha subunit of e. Coli replicative DNA polymerase iii
Structure: DNA polymerase iii alpha subunit. Chain: a. Fragment: catalytic fragment (residues 1-917). Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: dnae. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Monomer (from PQS)
2.60Å     R-factor:   0.223     R-free:   0.287
Authors: M.H.Lamers,R.E.Georgescu,S.G.Lee,M.O'Donnell,J.Kuriyan
Key ref:
M.H.Lamers et al. (2006). Crystal structure of the catalytic alpha subunit of E. coli replicative DNA polymerase III. Cell, 126, 881-892. PubMed id: 16959568 DOI: 10.1016/j.cell.2006.07.028
18-Jul-06     Release date:   19-Sep-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P10443  (DPO3A_ECOLI) -  DNA polymerase III subunit alpha
1160 a.a.
910 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
+ DNA(n)
Bound ligand (Het Group name = PO4)
matches with 55.56% similarity
+ 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     catalytic activity     4 terms  


DOI no: 10.1016/j.cell.2006.07.028 Cell 126:881-892 (2006)
PubMed id: 16959568  
Crystal structure of the catalytic alpha subunit of E. coli replicative DNA polymerase III.
M.H.Lamers, R.E.Georgescu, S.G.Lee, M.O'Donnell, J.Kuriyan.
Bacterial replicative DNA polymerases such as Polymerase III (Pol III) share no sequence similarity with other polymerases. The crystal structure, determined at 2.3 A resolution, of a large fragment of Pol III (residues 1-917), reveals a unique chain fold with localized similarity in the catalytic domain to DNA polymerase beta and related nucleotidyltransferases. The structure of Pol III is strikingly different from those of members of the canonical DNA polymerase families, which include eukaryotic replicative polymerases, suggesting that the DNA replication machinery in bacteria arose independently. A structural element near the active site in Pol III that is not present in nucleotidyltransferases but which resembles an element at the active sites of some canonical DNA polymerases suggests that, at a more distant level, all DNA polymerases may share a common ancestor. The structure also suggests a model for interaction of Pol III with the sliding clamp and DNA.
  Selected figure(s)  
Figure 1.
Figure 1. Overview of DNA Pol III Structure
(A) Top view in stereo and (B) side view in stereo. The location of the active site residues in the Palm domain are indicated by black spheres and the location of the phosphate ion in the PHP domain by red spheres. (C) The core region of Pol III alone resembles a cupped righthand shape. (PHP domain and ring and little Finger subdomains removed.)
Figure 4.
Figure 4. Pol III PHP Active Site Is Similar to that of DHH Phosphoesterases
(A) Surface representation showing PHP, Thumb, and Palm domains (similar view as in Figure 1B). A narrow groove runs from the Palm domain into a shallow cavity in the PHP domain that has phosphate bound. (B) Detailed view of shallow cavity in PHP domain is shown. (C) Active site of Streptococcus mutans PPase II (Merckel et al., 2001) is shown. Green sphere indicates a Mg^2+ ion and purple spheres Mn^2+ ions. The overall structure of this protein is unrelated to that of the PHP domain of Pol III.
  The above figures are reprinted by permission from Cell Press: Cell (2006, 126, 881-892) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21120860 T.Zeng, J.Li, and J.Liu (2011).
Distinct interfacial biclique patterns between ssDNA-binding proteins and those with dsDNAs.
  Proteins, 79, 598-610.  
20974932 B.Baños, L.Villar, M.Salas, and Vega (2010).
Intrinsic apurinic/apyrimidinic (AP) endonuclease activity enables Bacillus subtilis DNA polymerase X to recognize, incise, and further repair abasic sites.
  Proc Natl Acad Sci U S A, 107, 19219-19224.  
20615954 D.F.Warner, D.E.Ndwandwe, G.L.Abrahams, B.D.Kana, E.E.Machowski, C.Venclovas, and V.Mizrahi (2010).
Essential roles for imuA'- and imuB-encoded accessory factors in DnaE2-dependent mutagenesis in Mycobacterium tuberculosis.
  Proc Natl Acad Sci U S A, 107, 13093-13098.  
20184361 H.G.Dallmann, O.J.Fackelmayer, G.Tomer, J.Chen, A.Wiktor-Becker, T.Ferrara, C.Pope, M.T.Oliveira, P.M.Burgers, L.S.Kaguni, and C.S.McHenry (2010).
Parallel multiplicative target screening against divergent bacterial replicases: identification of specific inhibitors with broad spectrum potential.
  Biochemistry, 49, 2551-2562.  
20123134 J.D.Pata (2010).
Structural diversity of the Y-family DNA polymerases.
  Biochim Biophys Acta, 1804, 1124-1135.  
20413500 R.Reyes-Lamothe, D.J.Sherratt, and M.C.Leake (2010).
Stoichiometry and architecture of active DNA replication machinery in Escherichia coli.
  Science, 328, 498-501.  
19019142 E.Curti, J.P.McDonald, S.Mead, and R.Woodgate (2009).
DNA polymerase switching: effects on spontaneous mutagenesis in Escherichia coli.
  Mol Microbiol, 71, 315-331.  
19617571 J.M.Heltzel, R.W.Maul, S.K.Scouten Ponticelli, and M.D.Sutton (2009).
A model for DNA polymerase switching involving a single cleft and the rim of the sliding clamp.
  Proc Natl Acad Sci U S A, 106, 12664-12669.  
19966409 J.Sanchez-Weatherby, M.W.Bowler, J.Huet, A.Gobbo, F.Felisaz, B.Lavault, R.Moya, J.Kadlec, R.B.Ravelli, and F.Cipriani (2009).
Improving diffraction by humidity control: a novel device compatible with X-ray beamlines.
  Acta Crystallogr D Biol Crystallogr, 65, 1237-1246.
PDB codes: 2w6e 2w6f 2w6g 2w6h 2w6i 2w6j
19843218 J.Wagner, H.Etienne, R.P.Fuchs, A.Cordonnier, and D.Burnouf (2009).
Distinct beta-clamp interactions govern the activities of the Y family PolIV DNA polymerase.
  Mol Microbiol, 74, 1143-1151.  
19173290 M.J.McCauley, and M.C.Williams (2009).
Optical tweezers experiments resolve distinct modes of DNA-protein binding.
  Biopolymers, 91, 265-282.  
19251692 N.Leulliot, L.Cladière, F.Lecointe, D.Durand, U.Hübscher, and H.van Tilbeurgh (2009).
The Family X DNA Polymerase from Deinococcus radiodurans Adopts a Non-standard Extended Conformation.
  J Biol Chem, 284, 11992-11999.
PDB code: 2w9m
19696739 R.E.Georgescu, I.Kurth, N.Y.Yao, J.Stewart, O.Yurieva, and M.O'Donnell (2009).
Mechanism of polymerase collision release from sliding clamps on the lagging strand.
  EMBO J, 28, 2981-2991.  
19298182 S.M.Hamdan, and C.C.Richardson (2009).
Motors, switches, and contacts in the replisome.
  Annu Rev Biochem, 78, 205-243.  
19211662 S.Nakane, N.Nakagawa, S.Kuramitsu, and R.Masui (2009).
Characterization of DNA polymerase X from Thermus thermophilus HB8 reveals the POLXc and PHP domains are both required for 3'-5' exonuclease activity.
  Nucleic Acids Res, 37, 2037-2052.  
18776221 B.Baños, J.M.Lázaro, L.Villar, M.Salas, and Vega (2008).
Editing of misaligned 3'-termini by an intrinsic 3'-5' exonuclease activity residing in the PHP domain of a family X DNA polymerase.
  Nucleic Acids Res, 36, 5736-5749.  
18242150 H.Yang, and J.H.Miller (2008).
Deletion of dnaN1 generates a mutator phenotype in Bacillus anthracis.
  DNA Repair (Amst), 7, 507-514.  
18032433 J.Wardle, P.M.Burgers, I.K.Cann, K.Darley, P.Heslop, E.Johansson, L.J.Lin, P.McGlynn, J.Sanvoisin, C.M.Stith, and B.A.Connolly (2008).
Uracil recognition by replicative DNA polymerases is limited to the archaea, not occurring with bacteria and eukarya.
  Nucleic Acids Res, 36, 705-711.  
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
18834537 L.M.Iyer, S.Abhiman, and L.Aravind (2008).
A new family of polymerases related to superfamily A DNA polymerases and T7-like DNA-dependent RNA polymerases.
  Biol Direct, 3, 39.  
19106294 M.H.Lamers, and M.O'Donnell (2008).
A consensus view of DNA binding by the C family of replicative DNA polymerases.
  Proc Natl Acad Sci U S A, 105, 20565-20566.  
  18652472 M.J.McCauley, L.Shokri, J.Sefcikova, C.Venclovas, P.J.Beuning, and M.C.Williams (2008).
Distinct double- and single-stranded DNA binding of E. coli replicative DNA polymerase III alpha subunit.
  ACS Chem Biol, 3, 577-587.  
18931783 N.Y.Yao, and M.O'Donnell (2008).
Replisome dynamics and use of DNA trombone loops to bypass replication blocks.
  Mol Biosyst, 4, 1075-1084.  
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
18691598 R.A.Wing, S.Bailey, and T.A.Steitz (2008).
Insights into the replisome from the structure of a ternary complex of the DNA polymerase III alpha-subunit.
  J Mol Biol, 382, 859-869.
PDB code: 3e0d
19106298 R.J.Evans, D.R.Davies, J.M.Bullard, J.Christensen, L.S.Green, J.W.Guiles, J.D.Pata, W.K.Ribble, N.Janjic, and T.C.Jarvis (2008).
Structure of PolC reveals unique DNA binding and fidelity determinants.
  Proc Natl Acad Sci U S A, 105, 20695-20700.
PDB codes: 3f2b 3f2c 3f2d
18078545 C.D.Putnam, M.Hammel, G.L.Hura, and J.A.Tainer (2007).
X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution.
  Q Rev Biophys, 40, 191-285.  
17895578 F.Yanagihara, S.Yoshida, Y.Sugaya, and H.Maki (2007).
The dnaE173 mutator mutation confers on the alpha subunit of Escherichia coli DNA polymerase III a capacity for highly processive DNA synthesis and stable binding to primer/template DNA.
  Genes Genet Syst, 82, 273-280.  
18496613 M.Garcia-Diaz, and K.Bebenek (2007).
Multiple functions of DNA polymerases.
  CRC Crit Rev Plant Sci, 26, 105-122.  
17355988 S.Jergic, K.Ozawa, N.K.Williams, X.C.Su, D.D.Scott, S.M.Hamdan, J.A.Crowther, G.Otting, and N.E.Dixon (2007).
The unstructured C-terminus of the tau subunit of Escherichia coli DNA polymerase III holoenzyme is the site of interaction with the alpha subunit.
  Nucleic Acids Res, 35, 2813-2824.  
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
17176463 E.V.Koonin (2006).
Temporal order of evolution of DNA replication systems inferred by comparison of cellular and viral DNA polymerases.
  Biol Direct, 1, 39.  
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.