PDBsum entry 1ko9

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Hydrolase PDB id
Protein chain
312 a.a. *
SO4 ×2
Waters ×144
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Native structure of the human 8-oxoguanine DNA glycosylase hogg1
Structure: 8-oxoguanine DNA glycosylase. Chain: a. Synonym: n-glycosylase/DNA lyase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ogg1. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.15Å     R-factor:   0.206     R-free:   0.252
Authors: M.Bjoras,E.Seeberg,L.Luna,L.H.Pearl,T.E.Barrett
Key ref:
M.Bjørås et al. (2002). Reciprocal "flipping" underlies substrate recognition and catalytic activation by the human 8-oxo-guanine DNA glycosylase. J Mol Biol, 317, 171-177. PubMed id: 11902834 DOI: 10.1006/jmbi.2002.5400
20-Dec-01     Release date:   09-Jan-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
O15527  (OGG1_HUMAN) -  N-glycosylase/DNA lyase
345 a.a.
312 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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: 10.1006/jmbi.2002.5400 J Mol Biol 317:171-177 (2002)
PubMed id: 11902834  
Reciprocal "flipping" underlies substrate recognition and catalytic activation by the human 8-oxo-guanine DNA glycosylase.
M.Bjørås, E.Seeberg, L.Luna, L.H.Pearl, T.E.Barrett.
Both 8oxo-guanine and formamidopyrimidines are major products of oxidative DNA damage that can result in the fixation of transversion mutations following replication if left unrepaired. These lesions are targeted by the N-DNA glycosylase hOgg1, which catalyses excision of the aberrant base followed by cleavage of the phosphate backbone directly 5' to the resultant abasic site in a context, dependent manner. We present the crystal structure of native hOgg1 refined to 2.15 A resolution that reveals a number of highly significant conformational changes on association with DNA that are clearly required for substrate recognition and specificity. Changes of this magnitude appear to be unique to hOgg1 and have not been observed in any of the DNA-glycosylase structures analysed to date where both native and DNA-bound forms are available. It has been possible to identify a mechanism whereby the catalytic residue Lys 249 is "primed" for nucleophilic attack of the N-glycosidic bond.
  Selected figure(s)  
Figure 3.
Figure 3. Conformational changes on DNA binding. (a) The conformation of His270 in native and DNA- bound structures together with interactions involving Gln315, Phe319 and Asp322 which form a trigger mech- anism that switches between closed and open states of the 8oxoG binding pocket. (b) Changes occurring in both the 8oxoG and cytosine recognition sites are effected by residues in the interhelical segment along with Arg204 and Asn149. The most significant of these involves the side-chain amide oxygen atom of Asn149, which, in the native structure, forms a direct hydrogen bond to Lys249, but is flipped by 9 A to interact with the estranged cytosine base in the DNA-bound struc- ture. The protein in the complex structure has a Lys ! Gln mutation at position 249. (c) Hydrogen bonds from Asp268 and Asn149 to N e of Lys249 are both broken by the conformational changes that occur on DNA binding, leaving the catalytic lysine residue with a neutral amino group, ready for nucleophilic attack.
Figure 4.
Figure 4. Mutagenesis of Asp268. Mutation of Asp268 to either asparagine or alanine results in the almost complete abolition of 8oxoG cleavage activity that is consistent with Asp268 having a key catalytic role.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 317, 171-177) copyright 2002.  
  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
19537786 P.C.Anderson, and V.Daggett (2009).
The R46Q, R131Q and R154H polymorphs of human DNA glycosylase/beta-lyase hOgg1 severely distort the active site and DNA recognition site but do not cause unfolding.
  J Am Chem Soc, 131, 9506-9515.  
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.  
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.  
17114185 C.T.Radom, A.Banerjee, and G.L.Verdine (2007).
Structural characterization of human 8-oxoguanine DNA glycosylase variants bearing active site mutations.
  J Biol Chem, 282, 9182-9194.
PDB codes: 2nob 2noe 2nof 2noh 2noi 2nol 2noz
17090545 N.A.Kuznetsov, V.V.Koval, G.A.Nevinsky, K.T.Douglas, D.O.Zharkov, and O.S.Fedorova (2007).
Kinetic conformational analysis of human 8-oxoguanine-DNA glycosylase.
  J Biol Chem, 282, 1029-1038.  
16495121 V.L.Yip, and S.G.Withers (2006).
Breakdown of oligosaccharides by the process of elimination.
  Curr Opin Chem Biol, 10, 147-155.  
15642264 G.M.Lingaraju, A.A.Sartori, D.Kostrewa, A.E.Prota, J.Jiricny, and F.K.Winkler (2005).
A DNA glycosylase from Pyrobaculum aerophilum with an 8-oxoguanine binding mode and a noncanonical helix-hairpin-helix structure.
  Structure, 13, 87-98.
PDB codes: 1xqo 1xqp
15800211 L.Luna, V.Rolseth, G.A.Hildrestrand, M.Otterlei, F.Dantzer, M.Bjørås, and E.Seeberg (2005).
Dynamic relocalization of hOGG1 during the cell cycle is disrupted in cells harbouring the hOGG1-Cys326 polymorphic variant.
  Nucleic Acids Res, 33, 1813-1824.  
16024742 N.A.Kuznetsov, V.V.Koval, D.O.Zharkov, G.A.Nevinsky, K.T.Douglas, and O.S.Fedorova (2005).
Kinetics of substrate recognition and cleavage by human 8-oxoguanine-DNA glycosylase.
  Nucleic Acids Res, 33, 3919-3931.  
15102448 J.C.Fromme, A.Banerjee, and G.L.Verdine (2004).
DNA glycosylase recognition and catalysis.
  Curr Opin Struct Biol, 14, 43-49.  
14752045 P.A.van der Kemp, J.B.Charbonnier, M.Audebert, and S.Boiteux (2004).
Catalytic and DNA-binding properties of the human Ogg1 DNA N-glycosylase/AP lyase: biochemical exploration of H270, Q315 and F319, three amino acids of the 8-oxoguanine-binding pocket.
  Nucleic Acids Res, 32, 570-578.  
12644468 A.Jensen, G.Calvayrac, B.Karahalil, V.A.Bohr, and T.Stevnsner (2003).
Mammalian 8-oxoguanine DNA glycosylase 1 incises 8-oxoadenine opposite cytosine in nuclei and mitochondria, while a different glycosylase incises 8-oxoadenine opposite guanine in nuclei.
  J Biol Chem, 278, 19541-19548.  
12840008 J.C.Fromme, and G.L.Verdine (2003).
Structure of a trapped endonuclease III-DNA covalent intermediate.
  EMBO J, 22, 3461-3471.
PDB codes: 1orn 1orp 1p59
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
12034821 F.Dantzer, L.Luna, M.Bjørås, and E.Seeberg (2002).
Human OGG1 undergoes serine phosphorylation and associates with the nuclear matrix and mitotic chromatin in vivo.
  Nucleic Acids Res, 30, 2349-2357.  
12055620 J.C.Fromme, and G.L.Verdine (2002).
Structural insights into lesion recognition and repair by the bacterial 8-oxoguanine DNA glycosylase MutM.
  Nat Struct Biol, 9, 544-552.
PDB codes: 1l1t 1l1z 1l2b 1l2c 1l2d
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.