PDBsum entry 1dud

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Hydrolase PDB id
Protein chain
136 a.a. *
Waters ×94
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Deoxyuridine 5'-triphosphate nucleotide hydrolase (d-utpase) with the substrate analogue deoxyuridine 5'-diphosphate (d-
Structure: Deoxyuridine 5'-triphosphate nucleotidohydrolase. Chain: a. Ec:
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Trimer (from PDB file)
2.30Å     R-factor:   0.200    
Authors: G.Larsson,L.A.Svensson,P.O.Nyman
Key ref: G.Larsson et al. (1996). Crystal structure of the Escherichia coli dUTPase in complex with a substrate analogue (dUDP). Nat Struct Biol, 3, 532-538. PubMed id: 8646539
30-Apr-96     Release date:   08-Nov-96    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P06968  (DUT_ECOLI) -  Deoxyuridine 5'-triphosphate nucleotidohydrolase
151 a.a.
136 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - dUTP diphosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: dUTP + H2O = dUMP + diphosphate
Bound ligand (Het Group name = DUD)
matches with 85.71% similarity
+ H(2)O
= dUMP
+ diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytosol   1 term 
  Biological process     nucleotide metabolic process   4 terms 
  Biochemical function     hydrolase activity     4 terms  


Nat Struct Biol 3:532-538 (1996)
PubMed id: 8646539  
Crystal structure of the Escherichia coli dUTPase in complex with a substrate analogue (dUDP).
G.Larsson, L.A.Svensson, P.O.Nyman.
We have determined the structure of the homotrimeric dUTPase from Escherichia coli, completed with an inhibitor and substrate analogue, dUDP. Three molecules of dUDP are found symmetrically bound per trimer, each in a shallow cleft between adjacent subunits, interacting with evolutionary conserved residues. The interactions of the uracil ring and the deoxypentose with the protein are consistent with the high specificity of the enzyme with respect to these groups. The positions of the two phosphate groups and adjacent water molecules are discussed in relation to the mechanism and kinetics of catalysis. The role that dUTPase plays in DNA metabolism makes the enzyme a potential target for chemotherapeutic drugs: the results presented here will aid in the design and development of inhibitory compounds.

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20944217 G.W.Han, M.A.Elsliger, T.O.Yeates, Q.Xu, A.G.Murzin, S.S.Krishna, L.Jaroszewski, P.Abdubek, T.Astakhova, H.L.Axelrod, D.Carlton, C.Chen, H.J.Chiu, T.Clayton, D.Das, M.C.Deller, L.Duan, D.Ernst, J.Feuerhelm, J.C.Grant, A.Grzechnik, K.K.Jin, H.A.Johnson, H.E.Klock, M.W.Knuth, P.Kozbial, A.Kumar, W.W.Lam, D.Marciano, D.McMullan, M.D.Miller, A.T.Morse, E.Nigoghossian, L.Okach, R.Reyes, C.L.Rife, N.Sefcovic, H.J.Tien, C.B.Trame, H.van den Bedem, D.Weekes, K.O.Hodgson, J.Wooley, A.M.Deacon, A.Godzik, S.A.Lesley, and I.A.Wilson (2010).
Structure of a putative NTP pyrophosphohydrolase: YP_001813558.1 from Exiguobacterium sibiricum 255-15.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 66, 1237-1244.
PDB code: 3nl9
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.  
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.  
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
17549447 Y.Cho, H.S.Lee, Y.J.Kim, S.G.Kang, S.J.Kim, and J.H.Lee (2007).
Characterization of a dUTPase from the hyperthermophilic archaeon Thermococcus onnurineus NA1 and its application in polymerase chain reaction amplification.
  Mar Biotechnol (NY), 9, 450-458.  
16359314 M.Y.Galperin, O.V.Moroz, K.S.Wilson, and A.G.Murzin (2006).
House cleaning, a part of good housekeeping.
  Mol Microbiol, 59, 5.  
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
16014955 Y.Zhang, H.Moriyama, K.Homma, and J.L.Van Etten (2005).
Chlorella virus-encoded deoxyuridine triphosphatases exhibit different temperature optima.
  J Virol, 79, 9945-9953.  
14982624 E.A.Kouzminova, and A.Kuzminov (2004).
Chromosomal fragmentation in dUTPase-deficient mutants of Escherichia coli and its recombinational repair.
  Mol Microbiol, 51, 1279-1295.  
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
14724273 Z.Dubrovay, Z.Gáspári, E.Hunyadi-Gulyás, K.F.Medzihradszky, A.Perczel, and B.G.Vértessy (2004).
Multidimensional NMR identifies the conformational shift essential for catalytic competence in the 60-kDa Drosophila melanogaster dUTPase trimer.
  J Biol Chem, 279, 17945-17950.  
12721364 D.Mustafi, A.Bekesi, B.G.Vertessy, and M.W.Makinen (2003).
Catalytic and structural role of the metal ion in dUTP pyrophosphatase.
  Proc Natl Acad Sci U S A, 100, 5670-5675.  
12538648 H.Li, H.Xu, D.E.Graham, and R.H.White (2003).
The Methanococcus jannaschii dCTP deaminase is a bifunctional deaminase and diphosphatase.
  J Biol Chem, 278, 11100-11106.  
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.  
11782527 H.H.Hogrefe, C.J.Hansen, B.R.Scott, and K.B.Nielson (2002).
Archaeal dUTPase enhances PCR amplifications with archaeal DNA polymerases by preventing dUTP incorporation.
  Proc Natl Acad Sci U S A, 99, 596-601.  
12415291 M.J.Fogg, L.H.Pearl, and B.A.Connolly (2002).
Structural basis for uracil recognition by archaeal family B DNA polymerases.
  Nat Struct Biol, 9, 922-927.  
12021428 Y.Liu, and D.Eisenberg (2002).
3D domain swapping: as domains continue to swap.
  Protein Sci, 11, 1285-1299.  
  10438861 A.M.Baldo, and M.A.McClure (1999).
Evolution and horizontal transfer of dUTPase-encoding genes in viruses and their hosts.
  J Virol, 73, 7710-7721.  
  9847382 C.Abergel, D.L.Robertson, and J.M.Claverie (1999).
"Hidden" dUTPase sequence in human immunodeficiency virus type 1 gp120.
  J Virol, 73, 751-753.  
  10515998 M.Oliveros, R.García-Escudero, A.Alejo, E.Viñuela, M.L.Salas, and J.Salas (1999).
African swine fever virus dUTPase is a highly specific enzyme required for efficient replication in swine macrophages.
  J Virol, 73, 8934-8943.  
9497317 D.Prangishvili, H.P.Klenk, G.Jakobs, A.Schmiechen, C.Hanselmann, I.Holz, and W.Zillig (1998).
Biochemical and phylogenetic characterization of the dUTPase from the archaeal virus SIRV.
  J Biol Chem, 273, 6024-6029.  
9250362 J.M.Harris, R.H.Haynes, and E.M.McIntosh (1997).
A consensus sequence for a functional human endogenous retrovirus K (HERV-K) dUTPase.
  Biochem Cell Biol, 75, 143-151.  
  9151828 R.S.Weiss, M.O.Gold, H.Vogel, and R.T.Javier (1997).
Mutant adenovirus type 9 E4 ORF1 genes define three protein regions required for transformation of CREF cells.
  J Virol, 71, 4385-4394.  
  9311876 R.S.Weiss, and R.T.Javier (1997).
A carboxy-terminal region required by the adenovirus type 9 E4 ORF1 oncoprotein for transformation mediates direct binding to cellular polypeptides.
  J Virol, 71, 7873-7880.  
  9032316 R.S.Weiss, S.S.Lee, B.V.Prasad, and R.T.Javier (1997).
Human adenovirus early region 4 open reading frame 1 genes encode growth-transforming proteins that may be distantly related to dUTP pyrophosphatase enzymes.
  J Virol, 71, 1857-1870.  
8805593 C.D.Mol, J.M.Harris, E.M.McIntosh, and J.A.Tainer (1996).
Human dUTP pyrophosphatase: uracil recognition by a beta hairpin and active sites formed by three separate subunits.
  Structure, 4, 1077-1092.
PDB codes: 1q5h 1q5u
8994964 D.G.Vassylyev, and K.Morikawa (1996).
Precluding uracil from DNA.
  Structure, 4, 1381-1385.  
8798636 G.Larsson, P.O.Nyman, and J.O.Kvassman (1996).
Kinetic characterization of dUTPase from Escherichia coli.
  J Biol Chem, 271, 24010-24016.  
  8976551 G.S.Prasad, E.A.Stura, D.E.McRee, G.S.Laco, C.Hasselkus-Light, J.H.Elder, and C.D.Stout (1996).
Crystal structure of dUTP pyrophosphatase from feline immunodeficiency virus.
  Protein Sci, 5, 2429-2437.
PDB code: 1dut
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