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PDBsum entry 2i5w

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protein dna_rna ligands metals links
Hydrolase, lyase/DNA PDB id
2i5w
Jmol
Contents
Protein chain
311 a.a. *
DNA/RNA
Ligands
GOL
Metals
_CA ×2
Waters ×49
* Residue conservation analysis
PDB id:
2i5w
Name: Hydrolase, lyase/DNA
Title: Structure of hogg1 crosslinked to DNA sampling a normal g ad an oxog
Structure: 5'-d( Gp Gp Tp Ap Gp Ap Cp Cp Tp Gp Gp A)-3'. Chain: e. Engineered: yes. 5'-d(p Cp Cp Ap Gp (G42)p Tp Cp Tp Ap C)-3'. Chain: f. Engineered: yes. N-glycosylase/DNA lyase. Chain: a. Fragment: 8-oxoguanine DNA glycosylase, DNA-(apurinic or ap
Source: Synthetic: yes. Other_details: synthesized by solid phase DNA synthesis and subsequent manipulations.. Other_details: synthesized by solid phase DNA synthesis. Homo sapiens. Human. Organism_taxid: 9606. Gene: ogg1, mmh, mutm, ogh1. Expressed in: escherichia coli bl21(de3).
Biol. unit: Trimer (from PQS)
Resolution:
2.60Å     R-factor:   0.226     R-free:   0.266
Authors: A.Banerjee,G.L.Verdine
Key ref:
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. PubMed id: 17015827 DOI: 10.1073/pnas.0603644103
Date:
26-Aug-06     Release date:   17-Oct-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O15527  (OGG1_HUMAN) -  N-glycosylase/DNA lyase
Seq:
Struc:
345 a.a.
311 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: 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.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   6 terms 
  Biological process     metabolic process   19 terms 
  Biochemical function     catalytic activity     12 terms  

 

 
DOI no: 10.1073/pnas.0603644103 Proc Natl Acad Sci U S A 103:15020-15025 (2006)
PubMed id: 17015827  
 
 
A nucleobase lesion remodels the interaction of its normal neighbor in a DNA glycosylase complex.
A.Banerjee, G.L.Verdine.
 
  ABSTRACT  
 
How DNA glycosylases search through millions of base pairs and discriminate between rare sites of damage and otherwise undamaged bases is poorly understood. Even less understood are the details of the structural states arising from DNA glycosylases interacting with undamaged DNA. Recognizing the mutagenic lesion 7,8-dihydro-8-oxoguanine (8-oxoguanine, oxoG) represents an especially formidable challenge, because this oxidized nucleobase differs by only two atoms from its normal counterpart, guanine (G), and buried in the structure of naked B-form DNA, oxoG and G are practically indistinguishable from each other. We have used disulfide cross-linking technology to capture a human oxoG repair protein, 8-oxoguanine DNA glycosylase I (hOGG1) sampling an undamaged G:C base pair located adjacent to an oxoG:C base pair in DNA. The x-ray structure of the trapped complex reveals that the presence of the 8-oxoG drastically changes the local conformation of the extruded G. The extruded but intrahelical state of the G in this structure offers a view of an early intermediate in the base-extrusion pathway.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Overall structures of hOGG1–DNA complexes. In each structure, hOGG1 is represented as a blue ribbon trace and the bound DNA as a yellow ribbon-and-cylinders drawing. The target base in each is shown in a framework model, and its identity is denoted. (a) oxoG lesion-recognition complex (LRC) (11). (b) G complex (20). (c) oxoG|G complex.
Figure 5.
Fig. 5. Structural changes along the base-extrusion pathway of hOGG1. (a) Global changes in DNA structure. These figures were created by superposition of the protein component only of the LRC, G complex, and oxoG|G complex. The protein is not displayed, but the DNA bound to it is, with the color scheme as shown in the Inset. Note that the differences in conformation are limited to the target nucleoside (red) and right flank. (b and c) Protein-only superpositions of the protein–DNA interfaces, illustrating the similarities and differences in the interfaces. Contacts are denoted with hashed lines; blue for the oxoG|G complex and black for the LRC or the G complex; blue spheres, backbone amide NH atoms; W, ordered waters; oversized spheres, Ca^2+ ions. (b) oxoG|G complex versus G complex. (c) oxoG|G complex versus LRC.
 
  Figures were selected by the author.  
 
 
    Author's comment    
 
  This structure represents the earliest intermediate yet observed in the base-extrusion pathway of a DNA glycosylase, bacterial 8-oxoguanine DNA glycosylase (MutM or Fpg). The target base, a guanine, is extruded from the duplex helical stack, but is not extrahelical. This "intermediate" was captured using intermolecular disulfide crosslinking (DXL) technology (see Figure 1). The base-pair neigboring the extruded target target contains a fully intrahelical 8-oxoguanine (oxoG) lesion, and the presence of this lesion strongly influences the conformation of the target nucleoside; MutM is thus able to detect the presence of the lesion even when not sampling it directly.
Greg Verdine
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19889642 Y.Qi, M.C.Spong, K.Nam, M.Karplus, and G.L.Verdine (2010).
Entrapment and structure of an extrahelical guanine attempting to enter the active site of a bacterial DNA glycosylase, MutM.
  J Biol Chem, 285, 1468-1478.
PDB codes: 3jr4 3jr5
19674107 V.S.Sidorenko, A.P.Grollman, P.Jaruga, M.Dizdaroglu, and D.O.Zharkov (2009).
Substrate specificity and excision kinetics of natural polymorphic variants and phosphomimetic mutants of human 8-oxoguanine-DNA glycosylase.
  FEBS J, 276, 5149-5162.  
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
18072751 J.C.Delaney, and J.M.Essigmann (2008).
Biological properties of single chemical-DNA adducts: a twenty year perspective.
  Chem Res Toxicol, 21, 232-252.  
17581577 S.S.David, V.L.O'Shea, and S.Kundu (2007).
Base-excision repair of oxidative DNA damage.
  Nature, 447, 941-950.  
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.