PDBsum entry 3a6u

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Hydrolase PDB id
Protein chain
126 a.a. *
Waters ×92
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of mutt-8-oxo-dgmp-mn(ii) complex
Structure: Mutator mutt protein. Chain: a. Synonym: 7,8-dihydro-8-oxoguanine-triphosphatase, 8-oxo- dgtpase, dgtp pyrophosphohydrolase. Engineered: yes
Source: Escherichia coli k-12. Organism_taxid: 83333. Strain: k12. Gene: mutt. Expressed in: escherichia coli. Expression_system_taxid: 469008.
2.56Å     R-factor:   0.193     R-free:   0.242
Authors: T.Nakamura,Y.Yamagata
Key ref:
T.Nakamura et al. (2009). Structural and dynamic features of the MutT protein in the recognition of nucleotides with the mutagenic 8-oxoguanine base. J Biol Chem, 285, 444-452. PubMed id: 19864691 DOI: 10.1074/jbc.M109.066373
09-Sep-09     Release date:   27-Oct-09    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P08337  (MUTT_ECOLI) -  8-oxo-dGTP diphosphatase
129 a.a.
126 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 8-oxo-dGTP diphosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 8-oxo-dGTP + H2O = 8-oxo-dGMP + diphosphate
+ H(2)O
= 8-oxo-dGMP
+ diphosphate
      Cofactor: Mg(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     response to DNA damage stimulus   3 terms 
  Biochemical function     8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity     10 terms  


    Key reference    
DOI no: 10.1074/jbc.M109.066373 J Biol Chem 285:444-452 (2009)
PubMed id: 19864691  
Structural and dynamic features of the MutT protein in the recognition of nucleotides with the mutagenic 8-oxoguanine base.
T.Nakamura, S.Meshitsuka, S.Kitagawa, N.Abe, J.Yamada, T.Ishino, H.Nakano, T.Tsuzuki, T.Doi, Y.Kobayashi, S.Fujii, M.Sekiguchi, Y.Yamagata.
Escherichia coli MutT hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP event that can prevent the misincorporation of 8-oxoguanine opposite adenine in DNA. Of the several enzymes that recognize 8-oxoguanine, MutT exhibits high substrate specificity for 8-oxoguanine nucleotides; however, the structural basis for this specificity is unknown. The crystal structures of MutT in the apo and holo forms and in the binary and ternary forms complexed with the product 8-oxo-dGMP and 8-oxo-dGMP plus Mn(2+), respectively, were determined. MutT strictly recognizes the overall conformation of 8-oxo-dGMP through a number of hydrogen bonds. This recognition mode revealed that 8-oxoguanine nucleotides are discriminated from guanine nucleotides by not only the hydrogen bond between the N7-H and Odelta (N119) atoms but also by the syn glycosidic conformation that 8-oxoguanine nucleotides prefer. Nevertheless, these discrimination factors cannot by themselves explain the roughly 34,000-fold difference between the affinity of MutT for 8-oxo-dGMP and dGMP. When the binary complex of MutT with 8-oxo-dGMP is compared to the ligand-free form, ordering and considerable movement of the flexible loops surrounding 8-oxo-dGMP in the binary complex are observed. These results indicate that MutT specifically recognizes 8-oxoguanine nucleotides by the ligand-induced conformational change.
  Selected figure(s)  
Figure 2.
Crystal structures of MutT apo and MutT-8-oxo-dGMP complex forms. A, overall structure of MutT. α-Helices are in pink, and β-strands are in slate. A missing region of L-A is shown as a gray dashed line. B, overall structure of MutT-8-oxo-dGMP. 8-Oxo-dGMP is shown in ball and stick representation. C, comparison of the structures of the apo and complex forms. Apo and complex forms are shown in gray and slate, respectively. L-A and L-D regions in MutT-8-oxo-dGMP adopt a closed conformation as compared with those in the apo form.
Figure 3.
Recognition of 8-oxo-dGMP by MutT. A, hydrogen bonding interactions between 8-oxo-dGMP and loop regions (apo in gray and MutT-8-oxo-dGMP in slate). Amino acid residues involved in the hydrogen bonding interactions are shown in ball and stick representation. Water molecules are in red. Hydrogen bonds are shown as yellow dashed lines. B, the hydrophobic cave composed of β-1, β-3, β-3′, β-5, and α-2 is represented as a translucent surface (carbon in white, nitrogen in cyan, and oxygen in pink). C, interactions for the syn conformation of 8-oxo-dGMP. The hydrogen bond between Oδ of Asn-119 and N7-H of 8-oxoG is shown as a red dashed line. D, van der Waals interactions around the O8 atom. Amino acid residues recognizing O8 are shown in ball, stick, and translucent surface. E, a 2F[o] − F[c] electron density map around 8-oxo-dGMP contoured at 1.5 σ (stereo view).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2009, 285, 444-452) copyright 2009.  
  Figures were selected by an automated process.