PDBsum entry 1hu0

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protein dna_rna ligands metals links
Hydrolase/DNA PDB id
Protein chain
314 a.a. *
Waters ×98
* Residue conservation analysis
PDB id:
Name: Hydrolase/DNA
Title: Crystal structure of an hogg1-DNA borohydride trapped intermediate complex
Structure: 5'- d( Gp Gp Tp Ap Gp Ap Cp Cp Tp Gp Gp Ap Cp Gp C)-3'. Chain: d. Engineered: yes. 5'-d( Gp Cp Gp Tp Cp Cp Ap (Ped) p Gp Tp Cp Tp Ap Cp C)-3'. Chain: e. Engineered: yes. 8-oxoguanine DNA glycosylase 1.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: ogg1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PQS)
2.35Å     R-factor:   0.210     R-free:   0.245
Authors: J.C.Fromme,S.D.Bruner,W.Yang,M.Karplus,G.L.Verdine
Key ref:
J.C.Fromme et al. (2003). Product-assisted catalysis in base-excision DNA repair. Nat Struct Biol, 10, 204-211. PubMed id: 12592398 DOI: 10.1038/nsb902
03-Jan-01     Release date:   25-Feb-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
O15527  (OGG1_HUMAN) -  N-glycosylase/DNA lyase
345 a.a.
314 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 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: 10.1038/nsb902 Nat Struct Biol 10:204-211 (2003)
PubMed id: 12592398  
Product-assisted catalysis in base-excision DNA repair.
J.C.Fromme, S.D.Bruner, W.Yang, M.Karplus, G.L.Verdine.
Most spontaneous damage to bases in DNA is corrected through the action of the base-excision DNA repair pathway. Base excision repair is initiated by DNA glycosylases, lesion-specific enzymes that intercept aberrant bases in DNA and catalyze their excision. How such proteins accomplish the feat of catalyzing no fewer than five sequential reaction steps using a single active site has been unknown. To help answer this, we report the structure of a trapped catalytic intermediate in DNA repair by human 8-oxoguanine DNA glycosylase. This structure and supporting biochemical results reveal that the enzyme sequesters the excised lesion base and exploits it as a cofactor to participate in catalysis. To our knowledge, the present example represents the first documented case of product-assisted catalysis in an enzyme-catalyzed reaction.
  Selected figure(s)  
Figure 2.
Figure 2. Close-up view of the hOGG1 active site region. a, Stereo view showing a A^48-weighted 2F[o] - F[c] electron density map modeled at 1 , with elements of the protein and DNA in ball-and-stick models. The oxoG is red; Lys249, purple; DNA, gold; and the C-N bond between Lys249 of hOGG1 and C1' of the substrate, pink. b, Least-squares superposition of the active site region of the borohydride-trapped complex (same color scheme as in (a), except side chains are shown in teal) with that of the recognition complex with the K249Q mutation and an intact oxo-dG lesion21 (PDB entry 1EBM) (gray except Gln249, which is green).
Figure 3.
Figure 3. Interactions of the sequestered oxoG base with other components in the active site of the borohydride-trapped complex. a, Ball-and-stick representation of the X-ray structure. Color scheme is as in Fig. 2. b, Schematic depiction of the oxoG triangulated in position over the three atoms that are involved in acid/base chemistry during the -lyase cascade (N , O4' and C2'). Hydrogen bonding interactions are denoted by dashes. Dots indicate the distance between N9 and C2'. Note the distances between the N9 of oxoG and the O4' of the substrate sugar and the N of Lys249 in (a), indicative of hydrogen-bonding interactions. Also note the disposition of the proS and proR protons (denoted S and R, respectively) on C2' with respect to N9 and O8. The helix capping interaction between the side chain of Asp268 and the N terminus of helix M is clearly visible in (a).
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2003, 10, 204-211) copyright 2003.  
  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
21376058 M.K.Singh, K.Streu, A.J.McCrone, and B.N.Dominy (2011).
The Evolution of Catalytic Function in the HIV-1 Protease.
  J Mol Biol, 408, 792-805.  
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.  
18281210 A.D.Mackerell, and L.Nilsson (2008).
Molecular dynamics simulations of nucleic acid-protein complexes.
  Curr Opin Struct Biol, 18, 194-199.  
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
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.  
18557781 V.S.Sidorenko, G.V.Mechetin, G.A.Nevinsky, and D.O.Zharkov (2008).
Ionic strength and magnesium affect the specificity of Escherichia coli and human 8-oxoguanine-DNA glycosylases.
  FEBS J, 275, 3747-3760.  
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.  
17116430 T.K.Hazra, A.Das, S.Das, S.Choudhury, Y.W.Kow, and R.Roy (2007).
Oxidative DNA damage repair in mammalian cells: a new perspective.
  DNA Repair (Amst), 6, 470-480.  
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
16478987 K.K.Bhakat, S.K.Mokkapati, I.Boldogh, T.K.Hazra, and S.Mitra (2006).
Acetylation of human 8-oxoguanine-DNA glycosylase by p300 and its role in 8-oxoguanine repair in vivo.
  Mol Cell Biol, 26, 1654-1665.  
16495121 V.L.Yip, and S.G.Withers (2006).
Breakdown of oligosaccharides by the process of elimination.
  Curr Opin Chem Biol, 10, 147-155.  
15800616 A.Banerjee, W.Yang, M.Karplus, and G.L.Verdine (2005).
Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA.
  Nature, 434, 612-618.
PDB codes: 1yqk 1yql 1yqm 1yqr
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
15870208 M.Karplus, and J.Kuriyan (2005).
Molecular dynamics and protein function.
  Proc Natl Acad Sci U S A, 102, 6679-6685.  
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.  
14734554 A.Katafuchi, T.Nakano, A.Masaoka, H.Terato, S.Iwai, F.Hanaoka, and H.Ide (2004).
Differential specificity of human and Escherichia coli endonuclease III and VIII homologues for oxidative base lesions.
  J Biol Chem, 279, 14464-14471.  
15356290 H.P.Shanahan, M.A.Garcia, S.Jones, and J.M.Thornton (2004).
Identifying DNA-binding proteins using structural motifs and the electrostatic potential.
  Nucleic Acids Res, 32, 4732-4741.  
15102448 J.C.Fromme, A.Banerjee, and G.L.Verdine (2004).
DNA glycosylase recognition and catalysis.
  Curr Opin Struct Biol, 14, 43-49.  
14716003 M.Garcia-Viloca, J.Gao, M.Karplus, and D.G.Truhlar (2004).
How enzymes work: analysis by modern rate theory and computer simulations.
  Science, 303, 186-195.  
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.  
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.  
14527324 G.L.Verdine, and D.P.Norman (2003).
Covalent trapping of protein-DNA complexes.
  Annu Rev Biochem, 72, 337-366.  
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
12952961 R.Omi, M.Goto, I.Miyahara, H.Mizuguchi, H.Hayashi, H.Kagamiyama, and K.Hirotsu (2003).
Crystal structures of threonine synthase from Thermus thermophilus HB8: conformational change, substrate recognition, and mechanism.
  J Biol Chem, 278, 46035-46045.
PDB codes: 1uim 1uin 1uiq 1v7c
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.