PDBsum entry 1f7p

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Viral protein, hydrolase PDB id
Jmol PyMol
Protein chains
116 a.a. *
UDP ×2
Waters ×96
* Residue conservation analysis
PDB id:
Name: Viral protein, hydrolase
Title: Crystal structures of feline immunodeficiency virus dutp pyrophosphatase and its nucleotide complexes in three crystal forms.
Structure: Pol polyprotein. Chain: a, b, c. Fragment: dutpase. Engineered: yes
Source: Feline immunodeficiency virus. Organism_taxid: 11673. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.
Biol. unit: Trimer (from PQS)
2.30Å     R-factor:   0.221    
Authors: G.S.Prasad,E.A.Stura,J.H.Elder,C.D.Stout
Key ref:
G.S.Prasad et al. (2000). Structures of feline immunodeficiency virus dUTP pyrophosphatase and its nucleotide complexes in three crystal forms. Acta Crystallogr D Biol Crystallogr, 56, 1100-1109. PubMed id: 10957629 DOI: 10.1107/S0907444900009197
27-Jun-00     Release date:   06-Sep-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P16088  (POL_FIVPE) -  Pol polyprotein
1124 a.a.
116 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.  - RNA-directed Dna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
Deoxynucleoside triphosphate
Bound ligand (Het Group name = UDP)
matches with 55.00% similarity
+ DNA(n)
= diphosphate
+ DNA(n+1)
   Enzyme class 3: E.C.  - Exoribonuclease H.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Exonucleolytic cleavage to 5'-phosphomonoester oligonucleotides in both 5'- to 3'- and 3'- to 5'-directions.
   Enzyme class 4: E.C.  - Retroviral ribonuclease H.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
   Enzyme class 5: E.C.  - dUTP diphosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: dUTP + H2O = dUMP + diphosphate
+ H(2)O
= dUMP
+ diphosphate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
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  


DOI no: 10.1107/S0907444900009197 Acta Crystallogr D Biol Crystallogr 56:1100-1109 (2000)
PubMed id: 10957629  
Structures of feline immunodeficiency virus dUTP pyrophosphatase and its nucleotide complexes in three crystal forms.
G.S.Prasad, E.A.Stura, J.H.Elder, C.D.Stout.
dUTP pyrophosphatase (dUTPase) cleaves the alpha-beta phosphodiester of dUTP to form pyrophosphate and dUMP, preventing incorporation of uracil into DNA and providing the substrate for thymine synthesis. Seven crystal structures of feline immunodeficiency virus (FIV) dUTPase in three crystal forms have been determined, including complexes with substrate (dUTP), product (dUMP) or inhibitor (dUDP) bound. The native enzyme has been refined at 1.40 A resolution in a hexagonal crystal form and at 2.3 A resolution in an orthorhombic crystal form. In the dUDP complex in a cubic crystal form refined at 2.5 A resolution, the C-terminal conserved P-loop motif is fully ordered. The analysis defines the roles of five sequence motifs in interaction with uracil, deoxyribose and the alpha-, beta- and gamma-phosphates. The enzyme utilizes adaptive recognition to bind the alpha- and beta-phosphates. In particular, the alpha-beta phosphodiester adopts an unfavorable eclipsed conformation in the presence of the P-loop. This conformation may be relevant to the mechanism of alpha-beta phosphodiester bond cleavage.
  Selected figure(s)  
Figure 2.
Figure 2 Electron density for nucleotides in four unique FIV dUTPase complexes in three crystal forms (Table 2-). The maps were computed with 2|F[o]| - |F[c]| coefficients following simulated-annealing refinement and phase calculation in which the nucleotides were omitted. The maps are contoured at 1.0 and 3.0 . (a) The dUMP complex in the hexagonal crystal form. Copy A of the complex prepared by soaking in dUMP is shown. (b) The dUDP complex in the orthorhombic crystal form (copy A is shown). (c) The dUDP complex in the cubic crystal form. (d) The dUTP complex in the orthorhombic crystal form (copy A is shown).
Figure 4.
Figure 4 Interaction between FIV dUTPase and the phosphate groups of nucleotides in four unique complexes in three crystal forms (Table 2-). Potential hydrogen bonds (dotted lines) are indicated for all contacts [243]<= 3.5 between phosphate O atoms and protein atoms and for ordered H[2]O molecules. The asterisk indicates the O5' atom linking the [244][alpha] -phosphate to deoxyribose of the nucleotides. Roman numerals indicate the conserved sequence motifs to which the residues belong. (a) The dUMP complex in the hexagonal crystal form. Copy A of the complex prepared by soaking in dUMP is shown. (b) The dUDP complex in the orthorhombic crystal form (copy A is shown). (c) The dUDP complex in the cubic crystal form. (d) The dUTP complex in the orthorhombic crystal form (copy A is shown). For clarity, interactions of the [245][alpha] -phosphate with motif V are not shown.
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2000, 56, 1100-1109) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20823546 J.García-Nafría, L.Burchell, M.Takezawa, N.J.Rzechorzek, M.J.Fogg, and K.S.Wilson (2010).
The structure of the genomic Bacillus subtilis dUTPase: novel features in the Phe-lid.
  Acta Crystallogr D Biol Crystallogr, 66, 953-961.
PDB codes: 2xcd 2xce
18837522 B.G.Vértessy, and J.Tóth (2009).
Keeping uracil out of DNA: physiological role, structure and catalytic mechanism of dUTPases.
  Acc Chem Res, 42, 97.  
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
17932923 J.Kovári, O.Barabás, B.Varga, A.Békési, F.Tölgyesi, J.Fidy, J.Nagy, and B.G.Vértessy (2008).
Methylene substitution at the alpha-beta bridging position within the phosphate chain of dUDP profoundly perturbs ligand accommodation into the dUTPase active site.
  Proteins, 71, 308-319.
PDB codes: 2hr6 2hrm
17848562 J.Tóth, B.Varga, M.Kovács, A.Málnási-Csizmadia, and B.G.Vértessy (2007).
Kinetic mechanism of human dUTPase, an essential nucleotide pyrophosphatase enzyme.
  J Biol Chem, 282, 33572-33582.  
  17565183 M.Bajaj, and H.Moriyama (2007).
Purification, crystallization and preliminary crystallographic analysis of deoxyuridine triphosphate nucleotidohydrolase from Arabidopsis thaliana.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 409-411.
PDB code: 2pc5
17169987 V.Németh-Pongrácz, O.Barabás, M.Fuxreiter, I.Simon, I.Pichová, M.Rumlová, H.Zábranská, D.Svergun, M.Petoukhov, V.Harmat, E.Klement, E.Hunyadi-Gulyás, K.F.Medzihradszky, E.Kónya, and B.G.Vértessy (2007).
Flexible segments modulate co-folding of dUTPase and nucleocapsid proteins.
  Nucleic Acids Res, 35, 495-505.
PDB codes: 2d4l 2d4m 2d4n
15539408 E.Johansson, M.Fanø, J.H.Bynck, J.Neuhard, S.Larsen, B.W.Sigurskjold, U.Christensen, and M.Willemoës (2005).
Structures of dCTP deaminase from Escherichia coli with bound substrate and product: reaction mechanism and determinants of mono- and bifunctionality for a family of enzymes.
  J Biol Chem, 280, 3051-3059.
PDB codes: 1xs1 1xs4 1xs6
16154087 N.Tarbouriech, M.Buisson, J.M.Seigneurin, S.Cusack, and W.P.Burmeister (2005).
The monomeric dUTPase from Epstein-Barr virus mimics trimeric dUTPases.
  Structure, 13, 1299-1310.
PDB codes: 2bsy 2bt1
14724274 J.Kovári, O.Barabás, E.Takács, A.Békési, Z.Dubrovay, V.Pongrácz, I.Zagyva, T.Imre, P.Szabó, and B.G.Vértessy (2004).
Altered active site flexibility and a structural metal-binding site in eukaryotic dUTPase: kinetic characterization, folding, and crystallographic studies of the homotrimeric Drosophila enzyme.
  J Biol Chem, 279, 17932-17944.  
15208312 O.Barabás, V.Pongrácz, J.Kovári, M.Wilmanns, and B.G.Vértessy (2004).
Structural insights into the catalytic mechanism of phosphate ester hydrolysis by dUTPase.
  J Biol Chem, 279, 42907-42915.
PDB codes: 1rn8 1rnj 1seh 1syl
12756253 E.Johansson, O.Bjornberg, P.O.Nyman, and S.Larsen (2003).
Structure of the bifunctional dCTP deaminase-dUTPase from Methanocaldococcus jannaschii and its relation to other homotrimeric dUTPases.
  J Biol Chem, 278, 27916-27922.
PDB code: 1ogh
12869552 O.Barabás, M.Rumlová, A.Erdei, V.Pongrácz, I.Pichová, and B.G.Vértessy (2003).
dUTPase and nucleocapsid polypeptides of the Mason-Pfizer monkey virus form a fusion protein in the virion with homotrimeric organization and low catalytic efficiency.
  J Biol Chem, 278, 38803-38812.  
11420444 F.Hidalgo-Zarco, A.G.Camacho, V.Bernier-Villamor, J.Nord, L.M.Ruiz-Pérez, and D.González-Pacanowska (2001).
Kinetic properties and inhibition of the dimeric dUTPase-dUDPase from Leishmania major.
  Protein Sci, 10, 1426-1433.  
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.