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

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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.

Details

Authors
  • Gunilla Larsson
  • L Anders Svensson
  • Per-Olof Nyman
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biological Sciences
Original languageEnglish
Pages (from-to)532-538
JournalNature Structural & Molecular Biology
Volume3
Issue number6
Publication statusPublished - 1996
Publication categoryResearch
Peer-reviewedYes