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PDBsum entry 3a45

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protein metals Protein-protein interface(s) links
Hydrolase PDB id
3a45
Jmol PyMol
Contents
Protein chains
288 a.a. *
Metals
__K ×2
Waters ×531
* Residue conservation analysis
PDB id:
3a45
Name: Hydrolase
Title: Crystal structure of mvnei1_2
Structure: Formamidopyrimidine-DNA glycosylase. Chain: a, b. Synonym: fapy-DNA glycosylase, DNA-(apurinic or apyrimidinic site) lyase, ap lyase, endonuclease viii, mvnei1. Engineered: yes
Source: Acanthamoeba polyphaga mimivirus. Apmv. Organism_taxid: 212035. Gene: l315. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.30Å     R-factor:   0.203     R-free:   0.265
Authors: K.Imamura,S.Wallace,S.Doublie
Key ref:
K.Imamura et al. (2009). Structural characterization of a viral NEIL1 ortholog unliganded and bound to abasic site-containing DNA. J Biol Chem, 284, 26174-26183. PubMed id: 19625256 DOI: 10.1074/jbc.M109.021907
Date:
30-Jun-09     Release date:   21-Jul-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q5UQ00  (FPG_MIMIV) -  Probable formamidopyrimidine-DNA glycosylase
Seq:
Struc:
287 a.a.
288 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.3.2.2.23  - DNA-formamidopyrimidine glycosylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of DNA containing ring-opened N(7)-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimide.
   Enzyme class 2: E.C.4.2.99.18  - DNA-(apurinic or apyrimidinic site) lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     11 terms  

 

 
DOI no: 10.1074/jbc.M109.021907 J Biol Chem 284:26174-26183 (2009)
PubMed id: 19625256  
 
 
Structural characterization of a viral NEIL1 ortholog unliganded and bound to abasic site-containing DNA.
K.Imamura, S.S.Wallace, S.Doublié.
 
  ABSTRACT  
 
Endonuclease VIII (Nei) is a DNA glycosylase of the base excision repair pathway that recognizes and excises oxidized pyrimidines. We determined the crystal structures of a NEIL1 ortholog from the giant Mimivirus (MvNei1) unliganded and bound to DNA containing tetrahydrofuran (THF), which is the first structure of any Nei with an abasic site analog. The MvNei1 structures exhibit the same overall architecture as other enzymes of the Fpg/Nei family, which consists of two globular domains joined by a linker region. MvNei1 harbors a zincless finger, first described in human NEIL1, rather than the signature zinc finger generally found in the Fpg/Nei family. In contrast to Escherichia coli Nei, where a dramatic conformational change was observed upon binding DNA, the structure of MvNei1 bound to DNA does not reveal any substantial movement compared with the unliganded enzyme. A protein segment encompassing residues 217-245 in MvNei1 corresponds to the "missing loop" in E. coli Nei and the "alphaF-beta10 loop" in E. coli Fpg, which has been reported to be involved in lesion recognition. Interestingly, the corresponding loop in MvNei1 is ordered in both the unliganded and furan-bound structures, unlike other Fpg/Nei enzymes where the loop is generally ordered in the unliganded enzyme or in complexes with a lesion, and disordered otherwise. In the MvNei1.tetrahydrofuran complex a tyrosine located at the tip of the putative lesion recognition loop stacks against the furan ring; the tyrosine is predicted to adopt a different conformation to accommodate a modified base.
 
  Selected figure(s)  
 
Figure 2.
A, MvNei1·THF complex structure. The zincless finger, H2TH, catalytic proline and glutamic acid, and conserved arginine are highlighted in pink. The DNA is shown in gray. The putative lesion binding loop is shown in dark green. B, schematics of MvNei1·DNA interactions. Nucleotides are numbered beginning from THF0, with positive numbers toward the 5′-end. Hydrogen bonds are represented with black arrows pointing toward the acceptors. Tyr-221 stacks with THF.
Figure 3.
A, close-up view of THF and interacting residues with overlaid simulated annealing omit map contoured at 5 σ (lime green). MvNei1 is shown in green and DNA in gray. Hydrogen bonds are represented by black dashed lines. B, superposition of the MvNei1·THF complex onto LlaFpg·AP site complexes (THF and Pr). The MvNei1·THF complex is shown in green, LlaFpg/Pr complex (PDB code 1PJI (52)) in beige, and the LlaFpg·THF complex (PDB code 1PM5 (52)) in orange. The hydrogen bond is shown as a black dashed line. The blue dashed line indicates the distance between the amino group of Pro-2 and C1′ of THF.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2009, 284, 26174-26183) copyright 2009.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20172733 D.M.Wilson, and M.M.Seidman (2010).
A novel link to base excision repair?
  Trends Biochem Sci, 35, 247-252.  
21068368 J.Yeo, R.A.Goodman, N.T.Schirle, S.S.David, and P.A.Beal (2010).
RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1.
  Proc Natl Acad Sci U S A, 107, 20715-20719.  
20099873 X.Zhao, N.Krishnamurthy, C.J.Burrows, and S.S.David (2010).
Mutation versus repair: NEIL1 removal of hydantoin lesions in single-stranded, bulge, bubble, and duplex DNA contexts.
  Biochemistry, 49, 1658-1666.  
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.

 

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