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PDBsum entry 1pkh

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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
1pkh
Jmol
Contents
Protein chains
182 a.a. *
Ligands
EDO ×9
Waters ×361
* Residue conservation analysis
PDB id:
1pkh
Name: Hydrolase
Title: Structural basis for recognition and catalysis by the bifunctional dctp deaminase and dutpase from methanococcus jannaschii
Structure: Bifunctional deaminase/diphosphatase. Chain: a, b. Synonym: mjdcd-dut, dcd/dut. Engineered: yes
Source: Methanocaldococcus jannaschii. Organism_taxid: 2190. Gene: mj0430. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PQS)
Resolution:
1.42Å     R-factor:   0.186     R-free:   0.203
Authors: J.L.Huffman,H.Li,R.H.White,J.A.Tainer
Key ref:
J.L.Huffman et al. (2003). Structural basis for recognition and catalysis by the bifunctional dCTP deaminase and dUTPase from Methanococcus jannaschii. J Mol Biol, 331, 885-896. PubMed id: 12909016 DOI: 10.1016/S0022-2836(03)00789-7
Date:
05-Jun-03     Release date:   19-Aug-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q57872  (DCD_METJA) -  dCTP deaminase, dUMP-forming
Seq:
Struc:
204 a.a.
182 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.5.4.30  - dCTP deaminase (dUMP-forming).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: dCTP + 2 H2O = dUMP + diphosphate + NH3
dCTP
+ 2 × H(2)O
= dUMP
+ diphosphate
+ NH(3)
      Cofactor: Mg(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     nucleotide metabolic process   5 terms 
  Biochemical function     hydrolase activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0022-2836(03)00789-7 J Mol Biol 331:885-896 (2003)
PubMed id: 12909016  
 
 
Structural basis for recognition and catalysis by the bifunctional dCTP deaminase and dUTPase from Methanococcus jannaschii.
J.L.Huffman, H.Li, R.H.White, J.A.Tainer.
 
  ABSTRACT  
 
Potentially mutagenic uracil-containing nucleotide intermediates are generated by deamination of dCTP, either spontaneously or enzymatically as the first step in the conversion of dCTP to dTTP. dUTPases convert dUTP to dUMP, thus avoiding the misincorporation of dUTP into DNA and creating the substrate for the next enzyme in the dTTP synthetic pathway, thymidylate synthase. Although dCTP deaminase and dUTPase activities are usually found in separate but homologous enzymes, the hyperthermophile Methanococcus jannaschii has an enzyme, DCD-DUT, that harbors both dCTP deaminase and dUTP pyrophosphatase activities. DCD-DUT has highest activity on dCTP, followed by dUTP, and dTTP inhibits both the deaminase and pyrophosphatase activities. To help clarify structure-function relationships for DCD-DUT, we have determined the crystal structure of the wild-type DCD-DUT protein in its apo form to 1.42A and structures of DCD-DUT in complex with dCTP and dUTP to resolutions of 1.77A and 2.10A, respectively. To gain insights into substrate interactions, we complemented analyses of the experimentally defined weak density for nucleotides with automated docking experiments using dCTP, dUTP, and dTTP. DCD-DUT is a hexamer, unlike the homologous dUTPases, and its subunits contain several insertions and substitutions different from the dUTPase beta barrel core that likely contribute to dCTP specificity and deamination. These first structures of a dCTP deaminase reveal a probable role for an unstructured C-terminal region different from that of the dUTPases and possible mechanisms for both bifunctional enzyme activity and feedback inhibition by dTTP.
 
  Selected figure(s)  
 
Figure 7.
Figure 7. Proposed mechanism for DCD-DUT dCTP deamination.
Figure 8.
Figure 8. Docked DCD-DUT:dTTP inhibitory complex. (A) Interactions with the thymidine base, including Ile134, Phe138, and Ile142. (B) Repositioning of the sugar-phosphate moiety due to the proposed altered base conformation.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 331, 885-896) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18096851 L.L.Grochowski, and R.H.White (2008).
Promiscuous anaerobes: new and unconventional metabolism in methanogenic archaea.
  Ann N Y Acad Sci, 1125, 190-214.  
  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
15698576 J.L.Whittingham, I.Leal, C.Nguyen, G.Kasinathan, E.Bell, A.F.Jones, C.Berry, A.Benito, J.P.Turkenburg, E.J.Dodson, L.M.Ruiz Perez, A.J.Wilkinson, N.G.Johansson, R.Brun, I.H.Gilbert, D.Gonzalez Pacanowska, and K.S.Wilson (2005).
dUTPase as a platform for antimalarial drug design: structural basis for the selectivity of a class of nucleoside inhibitors.
  Structure, 13, 329-338.
PDB code: 1vyq
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.  
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.