PDBsum entry 1xsp

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protein dna_rna ligands metals links
Transferase/DNA PDB id
Protein chain
327 a.a. *
_NA ×4
Waters ×334
* Residue conservation analysis
PDB id:
Name: Transferase/DNA
Title: Crystal structure of human DNA polymerase lambda in complex with nicked DNA and pyrophosphate
Structure: 5'-d( Cp Gp Gp Cp Cp Gp Tp Ap Cp Tp G)-3'. Chain: t. Engineered: yes. 5'-d( Cp Ap Gp Tp Ap Cp G)-3'. Chain: p. Engineered: yes. 5'-d(p Gp Cp Cp G)-3'. Chain: d. Engineered: yes.
Source: Synthetic: yes. Other_details: template DNA. Other_details: primer DNA. Other_details: downstream primer DNA. Homo sapiens. Human. Organism_taxid: 9606. Gene: poll. Expressed in: escherichia coli.
Biol. unit: Tetramer (from PQS)
2.20Å     R-factor:   0.206     R-free:   0.242
Authors: M.Garcia-Diaz,K.Bebenek,J.M.Krahn,T.A.Kunkel,L.C.Pedersen
Key ref:
M.Garcia-Diaz et al. (2005). A closed conformation for the Pol lambda catalytic cycle. Nat Struct Mol Biol, 12, 97-98. PubMed id: 15608652 DOI: 10.1038/nsmb876
19-Oct-04     Release date:   18-Jan-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9UGP5  (DPOLL_HUMAN) -  DNA polymerase lambda
575 a.a.
327 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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 = PPV)
corresponds exactly
+ DNA(n+1)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     DNA repair   1 term 
  Biochemical function     DNA binding     4 terms  


DOI no: 10.1038/nsmb876 Nat Struct Mol Biol 12:97-98 (2005)
PubMed id: 15608652  
A closed conformation for the Pol lambda catalytic cycle.
M.Garcia-Diaz, K.Bebenek, J.M.Krahn, T.A.Kunkel, L.C.Pedersen.
Pol lambda is a family X member believed to fill short gaps during DNA repair. Here we report crystal structures of Pol lambda representing three steps in filling a single-nucleotide gap. These structures indicate that, unlike other DNA polymerases, Pol lambda does not undergo large subdomain movements during catalysis, and they provide a clear characterization of the geometry and stereochemistry of the in-line nucleotidyl transfer reaction.
  Selected figure(s)  
Figure 1.
Figure 1. Superimposition of the Pol structures. (a) The C traces of the binary (dark gray), nick ternary (green) and precatalytic ternary (orange) structures reveal two differences. One involves -strand 8 (ref. 10) (labeled A). The second involves -strands 3 and 4 (B; see text). Black lines indicate the span of the different subdomains: 8 kDa domain (8), fingers (F), palm (P) and thumb (T). (b) DNA shift upon dNTP binding. The DNA and part of the palm subdomain is shown for the binary (blue) and precatalytic ternary complex (yellow-brown). Hydrogen bonds, dashed lines; Mg2+ ion observed in the structure of the ternary complex, green.
Figure 2.
Figure 2. Conformational changes and nucleotidyl transfer catalysis. (a) Stereo representation of an overlay of the Pol active site in the binary (gray) and precatalytic ternary (brown) complex structures, focusing on the side chain movements observed upon dNTP binding. Hydrogen bonds, dashed lines. (b) Stereo view of the postcatalytic ternary complex. The two last bases of the primer strand and the catalytic carboxylates are shown, together with the pyrophosphate molecule. An overlay of the equivalent atoms in the structure of the precatalytic ternary complex is transparent. The line of transfer, dashed line. The 3' O that was the acceptor in the reaction (3'O[N]), the bridging oxygen of the leaving group (O[L]) and the phosphate (P ) are labeled.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2005, 12, 97-98) copyright 2005.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21233421 K.Bebenek, L.C.Pedersen, and T.A.Kunkel (2011).
Replication infidelity via a mismatch with Watson-Crick geometry.
  Proc Natl Acad Sci U S A, 108, 1862-1867.
PDB codes: 3pml 3pmn 3pnc
21377475 P.Xie (2011).
A model for the dynamics of mammalian family X DNA polymerases.
  J Theor Biol, 277, 111-122.  
19596089 E.A.Motea, and A.J.Berdis (2010).
Terminal deoxynucleotidyl transferase: the story of a misguided DNA polymerase.
  Biochim Biophys Acta, 1804, 1151-1166.  
19900463 J.A.Brown, K.A.Fiala, J.D.Fowler, S.M.Sherrer, S.A.Newmister, W.W.Duym, and Z.Suo (2010).
A novel mechanism of sugar selection utilized by a human X-family DNA polymerase.
  J Mol Biol, 395, 282-290.  
19631767 J.Yamtich, and J.B.Sweasy (2010).
DNA polymerase family X: function, structure, and cellular roles.
  Biochim Biophys Acta, 1804, 1136-1150.  
20435673 K.Bebenek, M.Garcia-Diaz, R.Z.Zhou, L.F.Povirk, and T.A.Kunkel (2010).
Loop 1 modulates the fidelity of DNA polymerase lambda.
  Nucleic Acids Res, 38, 5419-5431.
PDB codes: 3mgh 3mgi
21081096 Y.Li, and T.Schlick (2010).
Modeling DNA polymerase μ motions: subtle transitions before chemistry.
  Biophys J, 99, 3463-3472.  
19859523 C.Xu, B.A.Maxwell, J.A.Brown, L.Zhang, and Z.Suo (2009).
Global conformational dynamics of a Y-family DNA polymerase during catalysis.
  PLoS Biol, 7, e1000225.  
19502493 F.Romain, I.Barbosa, J.Gouge, F.Rougeon, and M.Delarue (2009).
Conferring a template-dependent polymerase activity to terminal deoxynucleotidyltransferase by mutations in the Loop1 region.
  Nucleic Acids Res, 37, 4642-4656.  
19806195 G.Terrados, J.P.Capp, Y.Canitrot, M.García-Díaz, K.Bebenek, T.Kirchhoff, A.Villanueva, F.Boudsocq, V.Bergoglio, C.Cazaux, T.A.Kunkel, J.S.Hoffmann, and L.Blanco (2009).
Characterization of a natural mutator variant of human DNA polymerase lambda which promotes chromosomal instability by compromising NHEJ.
  PLoS One, 4, e7290.  
19467241 J.D.Fowler, J.A.Brown, M.Kvaratskhelia, and Z.Suo (2009).
Probing conformational changes of human DNA polymerase lambda using mass spectrometry-based protein footprinting.
  J Mol Biol, 390, 368-379.  
19833706 K.Kuchta, L.Knizewski, L.S.Wyrwicz, L.Rychlewski, and K.Ginalski (2009).
Comprehensive classification of nucleotidyltransferase fold proteins: identification of novel families and their representatives in human.
  Nucleic Acids Res, 37, 7701-7714.  
19572669 M.C.Foley, and T.Schlick (2009).
Relationship between conformational changes in pol lambda's active site upon binding incorrect nucleotides and mismatch incorporation rates.
  J Phys Chem B, 113, 13035-13047.  
19701199 M.Garcia-Diaz, K.Bebenek, A.A.Larrea, J.M.Havener, L.Perera, J.M.Krahn, L.C.Pedersen, D.A.Ramsden, and T.A.Kunkel (2009).
Template strand scrunching during DNA gap repair synthesis by human polymerase lambda.
  Nat Struct Mol Biol, 16, 967-972.  
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
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.  
19598234 S.W.Fan, R.A.George, N.L.Haworth, L.L.Feng, J.Y.Liu, and M.A.Wouters (2009).
Conformational changes in redox pairs of protein structures.
  Protein Sci, 18, 1745-1765.  
19759017 W.A.Beard, D.D.Shock, V.K.Batra, L.C.Pedersen, and S.H.Wilson (2009).
DNA polymerase beta substrate specificity: side chain modulation of the "A-rule".
  J Biol Chem, 284, 31680-31689.
PDB codes: 3isb 3isc 3isd
17881298 J.M.Daley, and T.E.Wilson (2008).
Evidence that base stacking potential in annealed 3' overhangs determines polymerase utilization in yeast nonhomologous end joining.
  DNA Repair (Amst), 7, 67-76.  
18369368 K.Bebenek, M.Garcia-Diaz, M.C.Foley, L.C.Pedersen, T.Schlick, and T.A.Kunkel (2008).
Substrate-induced DNA strand misalignment during catalytic cycling by DNA polymerase lambda.
  EMBO Rep, 9, 459-464.
PDB codes: 3c5f 3c5g
18393274 K.H.Tang, and M.D.Tsai (2008).
Structure and function of 2:1 DNA polymerase.DNA complexes.
  J Cell Physiol, 216, 315-320.  
18385153 K.H.Tang, M.Niebuhr, C.S.Tung, H.C.Chan, C.C.Chou, and M.D.Tsai (2008).
Mismatched dNTP incorporation by DNA polymerase beta does not proceed via globally different conformational pathways.
  Nucleic Acids Res, 36, 2948-2957.
PDB code: 2van
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
18688254 U.Wimmer, E.Ferrari, P.Hunziker, and U.Hübscher (2008).
Control of DNA polymerase lambda stability by phosphorylation and ubiquitination during the cell cycle.
  EMBO Rep, 9, 1027-1033.  
18471977 V.K.Batra, W.A.Beard, D.D.Shock, L.C.Pedersen, and S.H.Wilson (2008).
Structures of DNA polymerase beta with active-site mismatches suggest a transient abasic site intermediate during misincorporation.
  Mol Cell, 30, 315-324.
PDB codes: 3c2k 3c2l 3c2m
17159995 A.F.Moon, M.Garcia-Diaz, K.Bebenek, B.J.Davis, X.Zhong, D.A.Ramsden, T.A.Kunkel, and L.C.Pedersen (2007).
Structural insight into the substrate specificity of DNA Polymerase mu.
  Nat Struct Mol Biol, 14, 45-53.
PDB code: 2ihm
17631059 A.F.Moon, M.Garcia-Diaz, V.K.Batra, W.A.Beard, K.Bebenek, T.A.Kunkel, S.H.Wilson, and L.C.Pedersen (2007).
The X family portrait: structural insights into biological functions of X family polymerases.
  DNA Repair (Amst), 6, 1709-1725.  
17666409 E.Crespan, U.Hübscher, and G.Maga (2007).
Error-free bypass of 2-hydroxyadenine by human DNA polymerase lambda with Proliferating Cell Nuclear Antigen and Replication Protein A in different sequence contexts.
  Nucleic Acids Res, 35, 5173-5181.  
18496613 M.Garcia-Diaz, and K.Bebenek (2007).
Multiple functions of DNA polymerases.
  CRC Crit Rev Plant Sci, 26, 105-122.  
17400246 P.R.Meyer, W.Rutvisuttinunt, S.E.Matsuura, A.G.So, and W.A.Scott (2007).
Stable complexes formed by HIV-1 reverse transcriptase at distinct positions on the primer-template controlled by binding deoxynucleoside triphosphates or foscarnet.
  J Mol Biol, 369, 41-54.  
16807316 A.J.Picher, M.García-Díaz, K.Bebenek, L.C.Pedersen, T.A.Kunkel, and L.Blanco (2006).
Promiscuous mismatch extension by human DNA polymerase lambda.
  Nucleic Acids Res, 34, 3259-3266.
PDB code: 2gws
16675458 K.A.Fiala, W.W.Duym, J.Zhang, and Z.Suo (2006).
Up-regulation of the fidelity of human DNA polymerase lambda by its non-enzymatic proline-rich domain.
  J Biol Chem, 281, 19038-19044.  
16920835 M.C.Foley, K.Arora, and T.Schlick (2006).
Sequential side-chain residue motions transform the binary into the ternary state of DNA polymerase lambda.
  Biophys J, 91, 3182-3195.  
16439207 M.Garcia-Diaz, K.Bebenek, J.M.Krahn, L.C.Pedersen, and T.A.Kunkel (2006).
Structural analysis of strand misalignment during DNA synthesis by a human DNA polymerase.
  Cell, 124, 331-342.
PDB codes: 2bcq 2bcr 2bcs 2bcu 2bcv
16545956 M.Garcia-Diaz, and T.A.Kunkel (2006).
Mechanism of a genetic glissando: structural biology of indel mutations.
  Trends Biochem Sci, 31, 206-214.  
16379496 O.Rechkoblit, L.Malinina, Y.Cheng, V.Kuryavyi, S.Broyde, N.E.Geacintov, and D.J.Patel (2006).
Stepwise translocation of Dpo4 polymerase during error-free bypass of an oxoG lesion.
  PLoS Biol, 4, e11.
PDB codes: 2asd 2asj 2asl 2atl 2au0
16963491 R.Juárez, J.F.Ruiz, S.A.Nick McElhinny, D.Ramsden, and L.Blanco (2006).
A specific loop in human DNA polymerase mu allows switching between creative and DNA-instructed synthesis.
  Nucleic Acids Res, 34, 4572-4582.  
17176036 R.Radhakrishnan, K.Arora, Y.Wang, W.A.Beard, S.H.Wilson, and T.Schlick (2006).
Regulation of DNA repair fidelity by molecular checkpoints: "gates" in DNA polymerase beta's substrate selection.
  Biochemistry, 45, 15142-15156.  
16615916 V.K.Batra, W.A.Beard, D.D.Shock, J.M.Krahn, L.C.Pedersen, and S.H.Wilson (2006).
Magnesium-induced assembly of a complete DNA polymerase catalytic complex.
  Structure, 14, 757-766.
PDB codes: 2fmp 2fmq 2fms
17005572 W.W.Duym, K.A.Fiala, N.Bhatt, and Z.Suo (2006).
Kinetic effect of a downstream strand and its 5'-terminal moieties on single nucleotide gap-filling synthesis catalyzed by human DNA polymerase lambda.
  J Biol Chem, 281, 35649-35655.  
16043633 E.Crespan, S.Zanoli, A.Khandazhinskaya, I.Shevelev, M.Jasko, L.Alexandrova, M.Kukhanova, G.Blanca, G.Villani, U.Hübscher, S.Spadari, and G.Maga (2005).
Incorporation of non-nucleoside triphosphate analogues opposite to an abasic site by human DNA polymerases beta and lambda.
  Nucleic Acids Res, 33, 4117-4127.  
16271888 L.G.Brieba, R.J.Kokoska, K.Bebenek, T.A.Kunkel, and T.Ellenberger (2005).
A lysine residue in the fingers subdomain of T7 DNA polymerase modulates the miscoding potential of 8-oxo-7,8-dihydroguanosine.
  Structure, 13, 1653-1659.
PDB code: 1zyq
16120966 S.González-Barrera, A.Sánchez, J.F.Ruiz, R.Juárez, A.J.Picher, G.Terrados, P.Andrade, and L.Blanco (2005).
Characterization of SpPol4, a unique X-family DNA polymerase in Schizosaccharomyces pombe.
  Nucleic Acids Res, 33, 4762-4774.  
16084394 V.K.Batra, W.A.Beard, D.D.Shock, L.C.Pedersen, and S.H.Wilson (2005).
Nucleotide-induced DNA polymerase active site motions accommodating a mutagenic DNA intermediate.
  Structure, 13, 1225-1233.
PDB codes: 1zjm 1zjn
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.