spacer
spacer

PDBsum entry 3mfi
Go to PDB code: 
protein dna_rna ligands metals links
Transferase/DNA PDB id
3mfi

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chain
511 a.a. *
DNA/RNA
Ligands
DTP
SO4 ×2
Metals
_MG ×2
Waters ×709
* Residue conservation analysis
PDB id:
3mfi
Name: Transferase/DNA
Title: DNA polymerase eta in complex with a cis-syn thymidine dimer
Structure: DNA polymerase eta. Chain: a. Fragment: unp residues 1-513. Synonym: radiation-sensitive protein 30. Engineered: yes. Mutation: yes. 5'-d( Gp Tp Cp Cp Tp Cp Cp Cp Cp Tp (Doc))-3'. Chain: p. Engineered: yes.
Source: Saccharomyces cerevisiae. Yeast. Organism_taxid: 4932. Gene: dbh1, rad30, ydr419w. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: oligonucleotide. Other_details: oligonucleotide
Resolution:
1.76Å     R-factor:   0.165     R-free:   0.187
Authors: T.D.Silverstein,R.E.Johnson,R.Jain,L.Prakash,S.Prakash,A.K.Aggarwal
Key ref: T.D.Silverstein et al. (2010). Structural basis for the suppression of skin cancers by DNA polymerase eta. Nature, 465, 1039-1043. PubMed id: 20577207
Date:
02-Apr-10     Release date:   23-Jun-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q04049  (POLH_YEAST) -  DNA polymerase eta from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Seq:
Struc: 		 
Seq:
Struc: 		632 a.a.
511 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DNA/RNA chains
  G-T-C-C-T-C-C-C-C-T-DOC 11 bases
  A-TTD-G-A-G-G-G-G-A-G-G-A-C 13 bases

 Enzyme reactions 
   Enzyme class: E.C.2.7.7.7  - DNA-directed Dna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
DNA(n)
 + 2'-deoxyribonucleoside 5'-triphosphate
 = DNA(n+1)
 + diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
Nature 465:1039-1043 (2010)
PubMed id: 20577207  
 
 
Structural basis for the suppression of skin cancers by DNA polymerase eta.
T.D.Silverstein, R.E.Johnson, R.Jain, L.Prakash, S.Prakash, A.K.Aggarwal.
 
  ABSTRACT  
 
DNA polymerase eta (Poleta) is unique among eukaryotic polymerases in its proficient ability for error-free replication through ultraviolet-induced cyclobutane pyrimidine dimers, and inactivation of Poleta (also known as POLH) in humans causes the variant form of xeroderma pigmentosum (XPV). We present the crystal structures of Saccharomyces cerevisiae Poleta (also known as RAD30) in ternary complex with a cis-syn thymine-thymine (T-T) dimer and with undamaged DNA. The structures reveal that the ability of Poleta to replicate efficiently through the ultraviolet-induced lesion derives from a simple and yet elegant mechanism, wherein the two Ts of the T-T dimer are accommodated in an active site cleft that is much more open than in other polymerases. We also show by structural, biochemical and genetic analysis that the two Ts are maintained in a stable configuration in the active site via interactions with Gln 55, Arg 73 and Met 74. Together, these features define the basis for Poleta's action on ultraviolet-damaged DNA that is crucial in suppressing the mutagenic and carcinogenic consequences of sun exposure, thereby reducing the incidence of skin cancers in humans.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
22562137 A.Ummat, O.Rechkoblit, R.Jain, J.Roy Choudhury, R.E.Johnson, T.D.Silverstein, A.Buku, S.Lone, L.Prakash, S.Prakash, and A.K.Aggarwal (2012).
Structural basis for cisplatin DNA damage tolerance by human polymerase η during cancer chemotherapy.
  Nat Struct Mol Biol, 19, 628-632.
PDB code: 4eey
21354175 R.Vasquez-Del Carpio, T.D.Silverstein, S.Lone, R.E.Johnson, L.Prakash, S.Prakash, and A.K.Aggarwal (2011).
Role of human DNA polymerase κ in extension opposite from a cis-syn thymine dimer.
  J Mol Biol, 408, 252-261.
PDB code: 3pzp
21258395 S.S.Lange, K.Takata, and R.D.Wood (2011).
DNA polymerases and cancer.
  Nat Rev Cancer, 11, 96.  
20660785 J.H.Yoon, G.Bhatia, S.Prakash, and L.Prakash (2010).
Error-free replicative bypass of thymine glycol by the combined action of DNA polymerases kappa and zeta in human cells.
  Proc Natl Acad Sci U S A, 107, 14116-14121.  
20934516 M.E.Arana, and T.A.Kunkel (2010).
Mutator phenotypes due to DNA replication infidelity.
  Semin Cancer Biol, 20, 304-311.  
  20936119 R.L.Eoff, J.Y.Choi, and F.P.Guengerich (2010).
Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage.
  J Nucleic Acids, 2010, 0.  
20577203 S.Broyde, and D.J.Patel (2010).
DNA repair: How to accurately bypass damage.
  Nature, 465, 1023-1024.  
  20936174 S.Chandani, C.Jacobs, and E.L.Loechler (2010).
Architecture of y-family DNA polymerases relevant to translesion DNA synthesis as revealed in structural and molecular modeling studies.
  J Nucleic Acids, 2010, 0.  
21076032 S.Schorr, S.Schneider, K.Lammens, K.P.Hopfner, and T.Carell (2010).
Mechanism of replication blocking and bypass of Y-family polymerase {eta} by bulky acetylaminofluorene DNA adducts.
  Proc Natl Acad Sci U S A, 107, 20720-20725.
PDB codes: 2xgp 2xgq
21070945 T.D.Silverstein, R.Jain, R.E.Johnson, L.Prakash, S.Prakash, and A.K.Aggarwal (2010).
Structural basis for error-free replication of oxidatively damaged DNA by yeast DNA polymerase η.
  Structure, 18, 1463-1470.
PDB codes: 3oha 3ohb
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 code is shown on the right.

 

spacer
spacer