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PDBsum entry 2okd

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
2okd
Jmol
Contents
Protein chains
124 a.a. *
Ligands
EDO ×4
Metals
_CL
Waters ×118
* Residue conservation analysis
PDB id:
2okd
Name: Hydrolase
Title: High resolution crystal structures of vaccinia virus dutpase
Structure: Deoxyuridine 5'-triphosphate nucleotidohydrolase. Chain: a, b, c. Synonym: dutpase, dutp pyrophosphatase. Engineered: yes
Source: Vaccinia virus. Organism_taxid: 10245. Gene: dut. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.40Å     R-factor:   0.209     R-free:   0.268
Authors: N.Schormann,D.Chattopadhyay
Key ref:
A.Samal et al. (2007). Structures of vaccinia virus dUTPase and its nucleotide complexes. Acta Crystallogr D Biol Crystallogr, 63, 571-580. PubMed id: 17452782 DOI: 10.1107/S0907444907007871
Date:
16-Jan-07     Release date:   01-May-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
A4GD96  (A4GD96_9POXV) -  DUTP pyrophosphatase
Seq:
Struc:
147 a.a.
124 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.6.1.23  - dUTP diphosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: dUTP + H2O = dUMP + diphosphate
dUTP
+ H(2)O
= dUMP
+ diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     dUTP metabolic process   1 term 
  Biochemical function     hydrolase activity     2 terms  

 

 
    reference    
 
 
DOI no: 10.1107/S0907444907007871 Acta Crystallogr D Biol Crystallogr 63:571-580 (2007)
PubMed id: 17452782  
 
 
Structures of vaccinia virus dUTPase and its nucleotide complexes.
A.Samal, N.Schormann, W.J.Cook, L.J.Delucas, D.Chattopadhyay.
 
  ABSTRACT  
 
Deoxyuridine triphosphate nucleotidohydrolase (dUTPase) catalyzes the hydrolysis of dUTP to dUMP and pyrophosphate in the presence of Mg(2+) ions. The enzyme plays multiple cellular roles by maintaining a low dUTP:dTTP ratio and by synthesizing the substrate for thymidylate synthase in the biosynthesis of dTTP. Although dUTPase is an essential enzyme and has been established as a valid target for drug design, the high degree of homology of vaccinia virus dUTPase to the human enzyme makes the identification of selective inhibitors difficult. The crystal structure of vaccinia virus dUTPase has been solved and the active site has been mapped by crystallographic analysis of the apo enzyme and of complexes with the substrate-analog dUMPNPP, with the product dUMP and with dUDP, which acts as an inhibitor. Analyses of these structures reveal subtle differences between the viral and human enzymes. In particular, the much larger size of the central channel at the trimer interface suggests new possibilities for structure-based drug design. Vaccinia virus is a prototype of the poxviruses.
 
  Selected figure(s)  
 
Figure 2.
Figure 2 Close-up view of the active sites in nucleotide complexes of vvdUTPase. The protein residues and ligands in the active sites of the protein-nucleotide complexes in full-length vvdUTPase are shown. (a) Superimposition of active sites in protein-nucleotide complexes (stereo figure). Color codes for the protein residues are red for the dUMPNPP complex (PDB code 2oke ), green for the dUMP complex (2ol1 ) and aquamarine for the dUDP complex (2ol0 ). Color codes for the ligands are orange for dUMPNPP, magenta for dUMP and wheat for dUDP. A few residues that show different rotamer conformations in the three nucleotide complexes are labeled. (b) Protein-dUMPNPP complex (F[o] - F[c] OMIT map contoured at 3 ). (c) Protein-dUMP complex (F[o] - F[c] OMIT map contoured at 3 ). (d) Protein-dUDP complex (F[o] - F[c] OMIT map contoured at 3 ). This figure was prepared with PyMOL (DeLano Scientific LLC).
Figure 3.
Figure 3 Superimposition of the active sites in dUDP complexes of human (PDB code 1q5h ) and vaccinia virus (PDB code 2ol0 ) dUTPase. The protein residues and the ligand(s) in the active site(s) of the dUDP complexes for vvdUTPase and human dUTPase are shown (stereo figure). Three residues in the active site that differ between 1q5h and 2ol0 are labeled. In addition, two Arg residues with different rotamer conformations are also labeled. Color codes for the protein residues are cyan, vvdUTPase; green, human dUTPase. Color codes for the ligands are salmon, vvdUTPase; yellow, human dUTPase. This figure was prepared with PyMOL (DeLano Scientific LLC).
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2007, 63, 571-580) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  19342774 G.L.Li, J.Wang, L.F.Li, and X.D.Su (2009).
Crystallization and preliminary X-ray analysis of three dUTPases from Gram-positive bacteria.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 339-342.  
  19851015 K.Homma, and H.Moriyama (2009).
Crystallization and crystal-packing studies of Chlorella virus deoxyuridine triphosphatase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 1030-1034.
PDB codes: 3c2t 3c3i 3ca9
19946139 K.Van Vliet, M.R.Mohamed, L.Zhang, N.Y.Villa, S.J.Werden, J.Liu, and G.McFadden (2009).
Poxvirus proteomics and virus-host protein interactions.
  Microbiol Mol Biol Rev, 73, 730-749.  
19586911 L.Freeman, M.Buisson, N.Tarbouriech, A.Van der Heyden, P.Labbé, and W.P.Burmeister (2009).
The flexible motif V of Epstein-Barr virus deoxyuridine 5'-triphosphate pyrophosphatase is essential for catalysis.
  J Biol Chem, 284, 25280-25289.
PDB codes: 2we0 2we1 2we2 2we3
  19055736 F.S.De Silva, and B.Moss (2008).
Effects of vaccinia virus uracil DNA glycosylase catalytic site and deoxyuridine triphosphatase deletion mutations individually and together on replication in active and quiescent cells and pathogenesis in mice.
  Virol J, 5, 145.  
  18321387 M.N.Prichard, E.R.Kern, D.C.Quenelle, K.A.Keith, R.W.Moyer, and P.C.Turner (2008).
Vaccinia virus lacking the deoxyuridine triphosphatase gene (F2L) replicates well in vitro and in vivo, but is hypersensitive to the antiviral drug (N)-methanocarbathymidine.
  Virol J, 5, 39.  
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.