PDBsum entry 2noi

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protein dna_rna metals links
Hydrolase, lyase/DNA PDB id
Protein chain
313 a.a. *
Waters ×142
* Residue conservation analysis
PDB id:
Name: Hydrolase, lyase/DNA
Title: Structure of g42a human 8-oxoguanine glycosylase crosslinked to undamaged g-containing DNA
Structure: 5'- d( Gp Gp Tp Ap Gp Ap Cp Cp Tp Gp Gp Ap Cp Gp C)-3'. Chain: b. Engineered: yes. 5'- d( Gp Cp Gp Tp C Cp Ap Gp Gp Tp Cp Tp Ap Cp C)-3'. Chain: c. Engineered: yes. N-glycosylase/DNA lyase.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: ogg1, mmh, mutm, ogh1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Trimer (from PQS)
2.35Å     R-factor:   0.226     R-free:   0.259
Authors: C.T.Radom,A.Banerjee,G.L.Verdine
Key ref:
C.T.Radom et al. (2007). Structural characterization of human 8-oxoguanine DNA glycosylase variants bearing active site mutations. J Biol Chem, 282, 9182-9194. PubMed id: 17114185 DOI: 10.1074/jbc.M608989200
25-Oct-06     Release date:   21-Nov-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
O15527  (OGG1_HUMAN) -  N-glycosylase/DNA lyase
345 a.a.
313 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 7 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - 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   5 terms 
  Biological process     metabolic process   21 terms 
  Biochemical function     catalytic activity     12 terms  


DOI no: 10.1074/jbc.M608989200 J Biol Chem 282:9182-9194 (2007)
PubMed id: 17114185  
Structural characterization of human 8-oxoguanine DNA glycosylase variants bearing active site mutations.
C.T.Radom, A.Banerjee, G.L.Verdine.
The human 8-oxoguanine DNA glycosylase (hOGG1) protein is responsible for initiating base excision DNA repair of the endogenous mutagen 8-oxoguanine. Like nearly all DNA glycosylases, hOGG1 extrudes its substrate from the DNA helix and inserts it into an extrahelical enzyme active site pocket lined with residues that participate in lesion recognition and catalysis. Structural analysis has been performed on mutant versions of hOGG1 having changes in catalytic residues but not on variants having altered 7,8-dihydro-8-oxoguanine (oxoG) contact residues. Here we report high resolution structural analysis of such recognition variants. We found that Ala substitution at residues that contact the phosphate 5' to the lesion (H270A mutation) and its Watson-Crick face (Q315A mutation) simply removed key functionality from the contact interface but otherwise had no effect on structure. Ala substitution at the only residue making an oxoG-specific contact (G42A mutation) introduced torsional stress into the DNA contact surface of hOGG1, but this was overcome by local interactions within the folded protein, indicating that this oxoG recognition motif is "hardwired." Introduction of a side chain intended to sterically obstruct the active site pocket (Q315F mutation) led to two different structures, one of which (Q315F(*149)) has the oxoG lesion in an exosite flanking the active site and the other of which (Q315F(*292)) has the oxoG inserted nearly completely into the lesion recognition pocket. The latter structure offers a view of the latest stage in the base extrusion pathway yet observed, and its lack of catalytic activity demonstrates that the transition state for displacement of the lesion base is geometrically demanding.
  Selected figure(s)  
Figure 2.
FIGURE 2. Effect of the H270A mutation. A, view of the active site region of the H270A structure (side chains in teal and DNA backbone in gold) showing four water molecules (green spheres) that coordinate the 5'-phosphate of oxoG to the protein with dashed lines denoting hydrogen bonds. B, least squares superposition showing the active site region of the H270A structure (colored as in A) with that of the proximally cross-linked recognition complex (LRC^*149; Protein Data Bank code 1YQR (28)) (white side chains and DNA backbone).
Figure 3.
FIGURE 3. Role of Gly-42 and consequences of the G42A mutation. A, stereoview of the G42A complex (protein chain in teal except for Ala-42, which is shown in magenta; DNA backbone in gold; and waters as green spheres) showing extensive hydrogen bonding interactions among residues of the Gly-42 loop and surrounding residues. B, schematic detailing the interactions from A. C, superposition of the G42A complex (colored as in A) with the LRC (protein and DNA in white and waters in gray). Inset, close-up view of the G42A complex showing the near eclipsing interaction of Ala-42 and the hydrogen bond formed between N7-H of oxoG and the carbonyl oxygen of Ala-42.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 9182-9194) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21220122 B.Dalhus, M.Forsbring, I.H.Helle, E.S.Vik, R.J.Forstrøm, P.H.Backe, I.Alseth, and M.Bjørås (2011).
Separation-of-function mutants unravel the dual-reaction mode of human 8-oxoguanine DNA glycosylase.
  Structure, 19, 117-127.
PDB code: 2xhi
20083120 F.Faucher, S.S.Wallace, and S.Doublié (2010).
The C-terminal lysine of Ogg2 DNA glycosylases is a major molecular determinant for guanine/8-oxoguanine distinction.
  J Mol Biol, 397, 46-56.
PDB code: 3knt
19446526 F.Faucher, S.Duclos, V.Bandaru, S.S.Wallace, and S.Doublié (2009).
Crystal structures of two archaeal 8-oxoguanine DNA glycosylases provide structural insight into guanine/8-oxoguanine distinction.
  Structure, 17, 703-712.
PDB codes: 3fhf 3fhg
19361427 F.Faucher, S.M.Robey-Bond, S.S.Wallace, and S.Doublié (2009).
Structural characterization of Clostridium acetobutylicum 8-oxoguanine DNA glycosylase in its apo form and in complex with 8-oxodeoxyguanosine.
  J Mol Biol, 387, 669-679.
PDB codes: 3f0z 3f10
19747886 F.Faucher, S.S.Wallace, and S.Doublié (2009).
Structural basis for the lack of opposite base specificity of Clostridium acetobutylicum 8-oxoguanine DNA glycosylase.
  DNA Repair (Amst), 8, 1283-1289.
PDB codes: 3i0w 3i0x
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.  
18507380 S.Lee, C.T.Radom, and G.L.Verdine (2008).
Trapping and structural elucidation of a very advanced intermediate in the lesion-extrusion pathway of hOGG1.
  J Am Chem Soc, 130, 7784-7785.  
18578506 S.M.Robey-Bond, R.Barrantes-Reynolds, J.P.Bond, S.S.Wallace, and V.Bandaru (2008).
Clostridium acetobutylicum 8-oxoguanine DNA glycosylase (Ogg) differs from eukaryotic Oggs with respect to opposite base discrimination.
  Biochemistry, 47, 7626-7636.  
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.  
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 code is shown on the right.