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Structure of the Bifunctional dCTP Deaminase-dUTPase from Methanocaldococcus jannaschii and Its Relation to Other Homotrimeric dUTPases

Johansson, Eva; Björnberg, Olof LU ; Nyman, Per-Olof LU and Larsen, Sine (2003) In Journal of Biological Chemistry 278(30). p.27916-27922
Abstract
The bifunctional dCTP deaminase-dUTPase (DCD-DUT) from Methanocaldococcus jannaschii catalyzes the deamination of the cytosine moiety in dCTP and the hydrolysis of the triphosphate moiety forming dUMP, thereby preventing uracil from being incorporated into DNA. The crystal structure of DCD-DUT has been determined to 1.88-Å resolution and represents the first known structure of an enzyme catalyzing dCTP deamination. The functional form of DCD-DUT is a homotrimer wherein the subunits are composed of a central distorted -barrel surrounded by two -sheets and four helices. The trimeric DCD-DUT shows structural similarity to trimeric dUTPases at the tertiary and quaternary levels. There are also additional structural elements in DCD-DUT compared... (More)
The bifunctional dCTP deaminase-dUTPase (DCD-DUT) from Methanocaldococcus jannaschii catalyzes the deamination of the cytosine moiety in dCTP and the hydrolysis of the triphosphate moiety forming dUMP, thereby preventing uracil from being incorporated into DNA. The crystal structure of DCD-DUT has been determined to 1.88-Å resolution and represents the first known structure of an enzyme catalyzing dCTP deamination. The functional form of DCD-DUT is a homotrimer wherein the subunits are composed of a central distorted -barrel surrounded by two -sheets and four helices. The trimeric DCD-DUT shows structural similarity to trimeric dUTPases at the tertiary and quaternary levels. There are also additional structural elements in DCD-DUT compared with dUTPase because of a longer primary structure. Four of the five conserved sequence motifs that create the active sites in dUTPase are found in structurally equivalent positions in DCD-DUT. The last 25 C-terminal residues of the 204-residue-long DCD-DUT are not visible in the electron density map, but, analogous to dUTPases, the C terminus is probably ordered, closing the active site upon catalysis. Unlike other enzymes catalyzing the deamination of cytosine compounds, DCD-DUT is not exploiting an enzyme-bound metal ion such as zinc or iron for nucleophile generation. The active site contains two water molecules that are engaged in hydrogen bonds to the invariant residues Ser118, Arg122, Thr130, and Glu145. These water molecules are potential nucleophile candidates in the deamination reaction. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
278
issue
30
pages
27916 - 27922
publisher
ASBMB
external identifiers
  • wos:000184242700074
  • scopus:0042847344
ISSN
1083-351X
DOI
language
English
LU publication?
yes
id
55dcbd32-9202-4844-8890-e65ee14474e8 (old id 124646)
date added to LUP
2007-07-05 13:30:04
date last changed
2018-05-29 10:06:43
@article{55dcbd32-9202-4844-8890-e65ee14474e8,
  abstract     = {The bifunctional dCTP deaminase-dUTPase (DCD-DUT) from Methanocaldococcus jannaschii catalyzes the deamination of the cytosine moiety in dCTP and the hydrolysis of the triphosphate moiety forming dUMP, thereby preventing uracil from being incorporated into DNA. The crystal structure of DCD-DUT has been determined to 1.88-Å resolution and represents the first known structure of an enzyme catalyzing dCTP deamination. The functional form of DCD-DUT is a homotrimer wherein the subunits are composed of a central distorted -barrel surrounded by two -sheets and four helices. The trimeric DCD-DUT shows structural similarity to trimeric dUTPases at the tertiary and quaternary levels. There are also additional structural elements in DCD-DUT compared with dUTPase because of a longer primary structure. Four of the five conserved sequence motifs that create the active sites in dUTPase are found in structurally equivalent positions in DCD-DUT. The last 25 C-terminal residues of the 204-residue-long DCD-DUT are not visible in the electron density map, but, analogous to dUTPases, the C terminus is probably ordered, closing the active site upon catalysis. Unlike other enzymes catalyzing the deamination of cytosine compounds, DCD-DUT is not exploiting an enzyme-bound metal ion such as zinc or iron for nucleophile generation. The active site contains two water molecules that are engaged in hydrogen bonds to the invariant residues Ser118, Arg122, Thr130, and Glu145. These water molecules are potential nucleophile candidates in the deamination reaction.},
  author       = {Johansson, Eva and Björnberg, Olof and Nyman, Per-Olof and Larsen, Sine},
  issn         = {1083-351X},
  language     = {eng},
  number       = {30},
  pages        = {27916--27922},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Structure of the Bifunctional dCTP Deaminase-dUTPase from Methanocaldococcus jannaschii and Its Relation to Other Homotrimeric dUTPases},
  url          = {http://dx.doi.org/},
  volume       = {278},
  year         = {2003},
}