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PDBsum entry 1kfv

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protein dna_rna ligands metals Protein-protein interface(s) links
Hydrolase/DNA PDB id
1kfv
Jmol
Contents
Protein chains
264 a.a. *
DNA/RNA
Ligands
GOL ×2
Metals
_ZN ×2
Waters ×54
* Residue conservation analysis
PDB id:
1kfv
Name: Hydrolase/DNA
Title: Crystal structure of lactococcus lactis formamido-pyrimidine glycosylase (alias fpg or mutm) non covalently bound to an containing DNA.
Structure: 5'-d( Cp Tp Cp Tp Tp Tp (Pdi)p Tp Tp Tp Cp Tp C)- chain: d, g. Engineered: yes. Other_details: contains a 1,3 propanediol site (pdi). 5'-d( Gp Ap Gp Ap Ap Ap Cp Ap Ap Ap Gp Ap G)-3'. Chain: e, h. Engineered: yes. Formamido-pyrimidine DNA glycosylase. Chain: a, b.
Source: Synthetic: yes. Lactococcus lactis. Organism_taxid: 1358. Gene: mutm or fpg. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PQS)
Resolution:
2.55Å     R-factor:   0.251     R-free:   0.285
Authors: L.Serre,K.Pereira De Jesus,S.Boiteux,C.Zelwer,B.Castaing
Key ref:
L.Serre et al. (2002). Crystal structure of the Lactococcus lactis formamidopyrimidine-DNA glycosylase bound to an abasic site analogue-containing DNA. EMBO J, 21, 2854-2865. PubMed id: 12065399 DOI: 10.1093/emboj/cdf304
Date:
23-Nov-01     Release date:   14-Jun-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P42371  (FPG_LACLC) -  Formamidopyrimidine-DNA glycosylase
Seq:
Struc:
273 a.a.
264 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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: 10.1093/emboj/cdf304 EMBO J 21:2854-2865 (2002)
PubMed id: 12065399  
 
 
Crystal structure of the Lactococcus lactis formamidopyrimidine-DNA glycosylase bound to an abasic site analogue-containing DNA.
L.Serre, K.Pereira de Jésus, S.Boiteux, C.Zelwer, B.Castaing.
 
  ABSTRACT  
 
The formamidopyrimidine-DNA glycosylase (Fpg, MutM) is a bifunctional base excision repair enzyme (DNA glycosylase/AP lyase) that removes a wide range of oxidized purines, such as 8-oxoguanine and imidazole ring-opened purines, from oxidatively damaged DNA. The structure of a non-covalent complex between the Lactoccocus lactis Fpg and a 1,3-propanediol (Pr) abasic site analogue-containing DNA has been solved. Through an asymmetric interaction along the damaged strand and the intercalation of the triad (M75/R109/F111), Fpg pushes out the Pr site from the DNA double helix, recognizing the cytosine opposite the lesion and inducing a 60 degrees bend of the DNA. The specific recognition of this cytosine provides some structural basis for understanding the divergence between Fpg and its structural homologue endo nuclease VIII towards their substrate specificities. In addition, the modelling of the 8-oxoguanine residue allows us to define an enzyme pocket that may accommodate the extrahelical oxidized base.
 
  Selected figure(s)  
 
Figure 6.
Figure 6 Stereo view of Fpg contacts around the Pr abasic site analogue. Hydrogen bonds are indicated by dashed lines. DNA atoms are represented by orange ball-and-sticks, and mutagenesis targeted amino acids are underlined (see text for details). The figures were generated by Molscript (Kraulis et al., 1991) and Raster3-D (Merritt and Murphy, 1994).
Figure 8.
Figure 8 Recognition of the C20 opposite the Pr site by R109. Stereo view showing the intercalation of the Fpg triad by the minor groove and the pseudo-Watson−Crick interactions between R109 and C20. Hydrogen bonds are indicated by dashed lines. The atomic coordinates of the triad (M70/R99/F101) from the free TtFpg have been superposed and are represented by green ball-and-sticks. The figure was generated by Molscript (Kraulis et al., 1991) and Raster3-D (Merritt and Murphy, 1994).
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2002, 21, 2854-2865) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference Google scholar

  PubMed id Reference
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
19134198 K.L.Tibballs, O.H.Ambur, K.Alfsnes, H.Homberset, S.A.Frye, T.Davidsen, and T.Tønjum (2009).
Characterization of the meningococcal DNA glycosylase Fpg involved in base excision repair.
  BMC Microbiol, 9, 7.  
  20198181 M.Banach, and I.Roterman (2009).
Recognition of protein complexation based on hydrophobicity distribution.
  Bioinformation, 4, 98.  
19264809 P.A.van der Kemp, M.de Padula, G.Burguiere-Slezak, H.D.Ulrich, and S.Boiteux (2009).
PCNA monoubiquitylation and DNA polymerase eta ubiquitin-binding domain are required to prevent 8-oxoguanine-induced mutagenesis in Saccharomyces cerevisiae.
  Nucleic Acids Res, 37, 2549-2559.  
19217358 S.D.Kathe, R.Barrantes-Reynolds, P.Jaruga, M.R.Newton, C.J.Burrows, V.Bandaru, M.Dizdaroglu, J.P.Bond, and S.S.Wallace (2009).
Plant and fungal Fpg homologs are formamidopyrimidine DNA glycosylases but not 8-oxoguanine DNA glycosylases.
  DNA Repair (Amst), 8, 643-653.  
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
16497933 A.Banerjee, W.L.Santos, and G.L.Verdine (2006).
Structure of a DNA glycosylase searching for lesions.
  Science, 311, 1153-1157.
PDB codes: 2f5n 2f5o 2f5p 2f5q 2f5s
16317709 C.Buré, B.Castaing, C.Lange, and A.F.Delmas (2006).
Location and base selectivity on fragmentation of brominated oligodeoxynucleotides.
  J Mass Spectrom, 41, 84-90.  
16928690 M.Rogacheva, A.Ishchenko, M.Saparbaev, S.Kuznetsova, and V.Ogryzko (2006).
High resolution characterization of formamidopyrimidine-DNA glycosylase interaction with its substrate by chemical cross-linking and mass spectrometry using substrate analogs.
  J Biol Chem, 281, 32353-32365.  
17115714 R.K.Walker, A.K.McCullough, and R.S.Lloyd (2006).
Uncoupling of nucleotide flipping and DNA bending by the t4 pyrimidine dimer DNA glycosylase.
  Biochemistry, 45, 14192-14200.  
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
15882618 J.R.Horton, K.Liebert, S.Hattman, A.Jeltsch, and X.Cheng (2005).
Transition from nonspecific to specific DNA interactions along the substrate-recognition pathway of dam methyltransferase.
  Cell, 121, 349-361.
PDB codes: 1yf3 1yfj 1yfl
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
15210696 B.B.Hopkins, and N.O.Reich (2004).
Simultaneous DNA binding, bending, and base flipping: evidence for a novel M.EcoRI methyltransferase-DNA complex.
  J Biol Chem, 279, 37049-37060.  
14607836 E.I.Zaika, R.A.Perlow, E.Matz, S.Broyde, R.Gilboa, A.P.Grollman, and D.O.Zharkov (2004).
Substrate discrimination by formamidopyrimidine-DNA glycosylase: a mutational analysis.
  J Biol Chem, 279, 4849-4861.  
15249553 F.Coste, M.Ober, T.Carell, S.Boiteux, C.Zelwer, and B.Castaing (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.
PDB codes: 1tdz 1xc8
15102448 J.C.Fromme, A.Banerjee, and G.L.Verdine (2004).
DNA glycosylase recognition and catalysis.
  Curr Opin Struct Biol, 14, 43-49.  
15178685 L.Larivière, and S.Moréra (2004).
Structural evidence of a passive base-flipping mechanism for beta-glucosyltransferase.
  J Biol Chem, 279, 34715-34720.
PDB codes: 1sxp 1sxq
15388802 M.de Padula, G.Slezak, P.Auffret van Der Kemp, and S.Boiteux (2004).
The post-replication repair RAD18 and RAD6 genes are involved in the prevention of spontaneous mutations caused by 7,8-dihydro-8-oxoguanine in Saccharomyces cerevisiae.
  Nucleic Acids Res, 32, 5003-5010.  
  15624311 N.Gillard, M.Begusova, B.Castaing, and M.Spotheim-Maurizot (2004).
Radiation affects binding of Fpg repair protein to an abasic site containing DNA.
  Radiat Res, 162, 566-571.  
15273302 P.Amara, L.Serre, B.Castaing, and A.Thomas (2004).
Insights into the DNA repair process by the formamidopyrimidine-DNA glycosylase investigated by molecular dynamics.
  Protein Sci, 13, 2009-2021.  
15232006 S.Doublié, V.Bandaru, J.P.Bond, and S.S.Wallace (2004).
The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity.
  Proc Natl Acad Sci U S A, 101, 10284-10289.
PDB code: 1tdh
14769949 V.V.Koval, N.A.Kuznetsov, D.O.Zharkov, A.A.Ishchenko, K.T.Douglas, G.A.Nevinsky, and O.S.Fedorova (2004).
Pre-steady-state kinetics shows differences in processing of various DNA lesions by Escherichia coli formamidopyrimidine-DNA glycosylase.
  Nucleic Acids Res, 32, 926-935.  
14661275 A.David, N.Bleimling, C.Beuck, J.M.Lehn, E.Weinhold, and M.P.Teulade-Fichou (2003).
DNA mismatch-specific base flipping by a bisacridine macrocycle.
  Chembiochem, 4, 1326-1331.  
12655006 F.Barone, E.Dogliotti, L.Cellai, C.Giordano, M.Bjørås, and F.Mazzei (2003).
Influence of DNA torsional rigidity on excision of 7,8-dihydro-8-oxo-2'-deoxyguanosine in the presence of opposing abasic sites by human OGG1 protein.
  Nucleic Acids Res, 31, 1897-1903.  
14527324 G.L.Verdine, and D.P.Norman (2003).
Covalent trapping of protein-DNA complexes.
  Annu Rev Biochem, 72, 337-366.  
14525999 J.C.Fromme, and G.L.Verdine (2003).
DNA lesion recognition by the bacterial repair enzyme MutM.
  J Biol Chem, 278, 51543-51548.
PDB codes: 1r2y 1r2z
12505993 K.D.Corbett, and J.M.Berger (2003).
Structure of the topoisomerase VI-B subunit: implications for type II topoisomerase mechanism and evolution.
  EMBO J, 22, 151-163.
PDB codes: 1mu5 1mx0
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.