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PDBsum entry 1tdz

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protein dna_rna ligands metals links
Hydrolase/DNA PDB id
1tdz
Jmol
Contents
Protein chain
265 a.a. *
DNA/RNA
Ligands
GOL
Metals
_ZN
Waters ×431
* Residue conservation analysis
PDB id:
1tdz
Name: Hydrolase/DNA
Title: Crystal structure complex between the lactococcus lactis fpg and a fapy-dg containing DNA
Structure: 5'-d( Cp Tp Cp Tp Tp Tp (Fox)p Tp Tp Tp Cp Tp Cp Chain: b. Engineered: yes. 5'-d( Gp Cp Gp Ap Gp Ap Ap Ap Cp Ap Ap Ap Gp A)-3 chain: c. Engineered: yes. Formamidopyrimidine-DNA glycosylase. Chain: a. Synonym: fapy-DNA glycosylase.
Source: Synthetic: yes. Lactococcus lactis. Organism_taxid: 1358. Gene: mutm, fpg. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PQS)
Resolution:
1.80Å     R-factor:   0.180     R-free:   0.207
Authors: F.Coste,M.Ober,T.Carell,S.Boiteux,C.Zelwer,B.Castaing
Key ref:
F.Coste et al. (2004). Structural basis for the recognition of the FapydG lesion (2,6-diamino-4-hydroxy-5-formamidopyrimidine) by formamidopyrimidine-DNA glycosylase. J Biol Chem, 279, 44074-44083. PubMed id: 15249553 DOI: 10.1074/jbc.M405928200
Date:
24-May-04     Release date:   07-Sep-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P42371  (FPG_LACLC) -  Formamidopyrimidine-DNA glycosylase
Seq:
Struc:
273 a.a.
265 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   6 terms 
  Biochemical function     catalytic activity     12 terms  

 

 
DOI no: 10.1074/jbc.M405928200 J Biol Chem 279:44074-44083 (2004)
PubMed id: 15249553  
 
 
Structural basis for the recognition of the FapydG lesion (2,6-diamino-4-hydroxy-5-formamidopyrimidine) by formamidopyrimidine-DNA glycosylase.
F.Coste, M.Ober, T.Carell, S.Boiteux, C.Zelwer, B.Castaing.
 
  ABSTRACT  
 
Formamidopyrimidine-DNA glycosylase (Fpg) is a DNA repair enzyme that excises oxidized purines such as 7,8-dihydro-8-oxoguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) from damaged DNA. Here, we report the crystal structure of the Fpg protein from Lactococcus lactis (LlFpg) bound to a carbocyclic FapydG (cFapydG)-containing DNA. The structure reveals that Fpg stabilizes the cFapydG nucleoside into an extrahelical conformation inside its substrate binding pocket. In contrast to the recognition of the 8-oxodG lesion, which is bound with the glycosidic bond in a syn conformation, the cFapydG lesion displays in the complex an anti conformation. Furthermore, Fpg establishes interactions with all the functional groups of the FapyG base lesion, which can be classified in two categories: (i) those specifying a purine-derived lesion (here a guanine) involved in the Watson-Crick face recognition of the lesion and probably contributing to an optimal orientation of the pyrimidine ring moiety in the binding pocket and (ii) those specifying the imidazole ring-opened moiety of FapyG and probably participating also in the rotameric selection of the FapydG nucleobase. These interactions involve strictly conserved Fpg residues and structural water molecules mediated interactions. The significant differences between the Fpg recognition modes of 8-oxodG and FapydG provide new insights into the Fpg substrate specificity.
 
  Selected figure(s)  
 
Figure 4.
FIG. 4. Interactions between the extrahelical cFapydG and Fpg residues inside the active site binding pocket. A, schematic representation of Fpg/DNA contacts at the target site. Amino acid residues of LlFpg involved in the recognition are shown in red and the DNA are shown in blue. C, the cytosine opposite cFapydG (G*). p0 and p-1 indicate the phosphate groups bordering the lesion. Small green circles represent the water-mediated interactions. Black dashed lines represent hydrogen bond interactions. B, stereoviews of the cFapydG recognition complex active site. The C- backbone of Fpg is in yellow, main chains and side chains of indicated Fpg residues are in yellow and pink, respectively. Covalent links are indicated by ball-and-sticks representation. Carbons of DNA are shown in gray, oxygen atoms in red, nitrogen atoms in blue, phosphate atoms in dark magenta, and sulfur atoms in orange. The water molecules (wat) mediating interactions between Fpg residues and the cFapydG functional groups are indicated by small red spheres. Inferred hydrogen bonds are shown as orange dashed lines. C, distances between hydrogen bond donors and acceptors indicated in B.
Figure 6.
FIG. 6. Superimposition of cFapydG (anti) and 8-oxodG (syn) nucleobases in the extrahelical base binding pocket of Fpg. Carbons of cFapydG and 8-oxodG are shown as gray and green spheres, respectively. The chemical mutation of the heterocycle oxygen (O4') of the deoxyribose in the -CH[2] group in the cyclopentane of cFapydG is indicated as the 6' position.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 44074-44083) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20563891 E.J.Petersen, and B.C.Nelson (2010).
Mechanisms and measurements of nanomaterial-induced oxidative damage to DNA.
  Anal Bioanal Chem, 398, 613-650.  
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.  
20540060 M.Winnacker, V.Welzmiller, R.Strasser, and T.Carell (2010).
Development of a DNA photoaffinity probe for the analysis of 8-OxodG-binding proteins in a human proteome.
  Chembiochem, 11, 1345-1349.  
19625256 K.Imamura, S.S.Wallace, and S.Doublié (2009).
Structural characterization of a viral NEIL1 ortholog unliganded and bound to abasic site-containing DNA.
  J Biol Chem, 284, 26174-26183.
PDB codes: 3a42 3a45 3a46
19397282 P.P.Christov, K.C.Angel, F.P.Guengerich, and C.J.Rizzo (2009).
Replication past the N5-methyl-formamidopyrimidine lesion of deoxyguanosine by DNA polymerases and an improved procedure for sequence analysis of in vitro bypass products by mass spectrometry.
  Chem Res Toxicol, 22, 1086-1095.  
19200715 S.Schneider, S.Schorr, and T.Carell (2009).
Crystal structure analysis of DNA lesion repair and tolerance mechanisms.
  Curr Opin Struct Biol, 19, 87-95.  
18682218 B.R.Bowman, S.Lee, S.Wang, and G.L.Verdine (2008).
Structure of the E. coli DNA glycosylase AlkA bound to the ends of duplex DNA: a system for the structure determination of lesion-containing DNA.
  Structure, 16, 1166-1174.
PDB codes: 3cvs 3cvt 3cw7 3cwa 3cws 3cwt 3cwu
18635007 F.Coste, M.Ober, Y.V.Le Bihan, M.A.Izquierdo, N.Hervouet, H.Mueller, T.Carell, and B.Castaing (2008).
Bacterial base excision repair enzyme Fpg recognizes bulky N7-substituted-FapydG lesion via unproductive binding mode.
  Chem Biol, 15, 706-717.
PDB code: 3c58
18506863 H.Mueller, M.Hopfinger, and T.Carell (2008).
Synthesis of a stabilized version of the imidazolone DNA lesion.
  Chembiochem, 9, 1617-1622.  
17551974 K.Song, V.Hornak, C.de los Santos, A.P.Grollman, and C.Simmerling (2008).
Molecular mechanics parameters for the FapydG DNA lesion.
  J Comput Chem, 29, 17-23.  
18692130 M.Dizdaroglu, G.Kirkali, and P.Jaruga (2008).
Formamidopyrimidines in DNA: mechanisms of formation, repair, and biological effects.
  Free Radic Biol Med, 45, 1610-1621.  
18154319 N.Krishnamurthy, K.Haraguchi, M.M.Greenberg, and S.S.David (2008).
Efficient removal of formamidopyrimidines by 8-oxoguanine glycosylases.
  Biochemistry, 47, 1043-1050.  
17382378 G.Frosina (2007).
Gene prophylaxis by a DNA repair function.
  Mol Aspects Med, 28, 323-344.  
17432829 L.Jia, V.Shafirovich, N.E.Geacintov, and S.Broyde (2007).
Lesion specificity in the base excision repair enzyme hNeil1: modeling and dynamics studies.
  Biochemistry, 46, 5305-5314.  
17655276 N.Krishnamurthy, J.G.Muller, C.J.Burrows, and S.S.David (2007).
Unusual structural features of hydantoin lesions translate into efficient recognition by Escherichia coli Fpg.
  Biochemistry, 46, 9355-9365.  
17015827 A.Banerjee, and G.L.Verdine (2006).
A nucleobase lesion remodels the interaction of its normal neighbor in a DNA glycosylase complex.
  Proc Natl Acad Sci U S A, 103, 15020-15025.
PDB code: 2i5w
16432839 G.Frosina (2006).
Prophylaxis of oxidative DNA damage by formamidopyrimidine-DNA glycosylase.
  Int J Cancer, 119, 1-7.  
16528786 R.P.Clausen (2006).
Organic chemistry at the interface to biology.
  Chembiochem, 7, 845-849.  
16145054 G.Golan, D.O.Zharkov, H.Feinberg, A.S.Fernandes, E.I.Zaika, J.H.Kycia, A.P.Grollman, and G.Shoham (2005).
Structure of the uncomplexed DNA repair enzyme endonuclease VIII indicates significant interdomain flexibility.
  Nucleic Acids Res, 33, 5006-5016.
PDB codes: 1q39 1q3b 1q3c
16243784 K.Pereira de Jésus, L.Serre, C.Zelwer, and B.Castaing (2005).
Structural insights into abasic site for Fpg specific binding and catalysis: comparative high-resolution crystallographic studies of Fpg bound to various models of abasic site analogues-containing DNA.
  Nucleic Acids Res, 33, 5936-5944.
PDB codes: 1nnj 1pji 1pjj 1pm5
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.