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Crystal structure of the Escherichia coli dUTPase in complex with a substrate analogue (dUDP)

Larsson, Gunilla; Svensson, L Anders and Nyman, Per-Olof LU (1996) In Nature Structural & Molecular Biology 3(6). p.532-538
Abstract
We have determined the structure of the homotrimeric dUTPase from Escherichia coli, complexed 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... (More)
We have determined the structure of the homotrimeric dUTPase from Escherichia coli, complexed 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Structural & Molecular Biology
volume
3
issue
6
pages
532 - 538
publisher
Nature Publishing Group
external identifiers
  • scopus:0029882967
ISSN
1545-9985
DOI
10.1038/nsb0696-532
language
English
LU publication?
yes
id
96686a3d-9a6f-4f6e-8c5e-b9832898bb28 (old id 126305)
date added to LUP
2007-07-06 12:03:02
date last changed
2017-01-01 06:41:41
@article{96686a3d-9a6f-4f6e-8c5e-b9832898bb28,
  abstract     = {We have determined the structure of the homotrimeric dUTPase from Escherichia coli, complexed 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.},
  author       = {Larsson, Gunilla and Svensson, L Anders and Nyman, Per-Olof},
  issn         = {1545-9985},
  language     = {eng},
  number       = {6},
  pages        = {532--538},
  publisher    = {Nature Publishing Group},
  series       = {Nature Structural & Molecular Biology},
  title        = {Crystal structure of the Escherichia coli dUTPase in complex with a substrate analogue (dUDP)},
  url          = {http://dx.doi.org/10.1038/nsb0696-532},
  volume       = {3},
  year         = {1996},
}