Altered subunit communication in subfamilies of trimeric dUTPases

Andras Fiser, B. G. Vértessy

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The enzyme dUTPase is essential in preventing uracil incorporation into DNA. Design of antagonist's against this novel chemotherapeutic target requires identification of species-specific differences in the structure and mechanism of the enzyme. This task is now approached via comparisons of available crystallographic structures of dUTPases from Homo sapiens, Escherichia coli, and retroviruses. The eukaryotic protein uniquely displays polar and charged amino acid residues participating in threefold intersubunit interactions. In bacterial and retroviral dUTPases, threefold interactions are mainly hydrophobic. The residues responsible for this contrast are mapped in multiple sequence alignment to positions differently and characteristically conserved in distinct evolutionary branches. The general feature of this contrast is further strengthened by a second eukaryotic model structure constructed using comparative modeling. The dUTPase cDNA from Drosophila melanogaster was identified, sequenced, and the model structure of the encoded polypeptide displayed a polar hydrogen-bonding network of threefold interactions, identically to the human structure. Results allow clear distinction between two subfamilies of trimeric dUTPases where altered subunit communication may account for a functional difference in the catalytic cycle.

Original languageEnglish (US)
Pages (from-to)534-542
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume279
Issue number2
DOIs
StatePublished - Dec 20 2000
Externally publishedYes

Fingerprint

Model structures
Communication
Uracil
Sequence Alignment
Retroviridae
Enzymes
Hydrogen Bonding
Drosophila melanogaster
Hydrophobic and Hydrophilic Interactions
Escherichia coli
Hydrogen bonds
Complementary DNA
Amino Acids
Peptides
DNA
Proteins
dUTP pyrophosphatase

Keywords

  • Allosterism
  • Comparative modeling
  • Drosophila melanogaster
  • dUTPase
  • Hydropathy
  • Intersubunit forces

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Altered subunit communication in subfamilies of trimeric dUTPases. / Fiser, Andras; Vértessy, B. G.

In: Biochemical and Biophysical Research Communications, Vol. 279, No. 2, 20.12.2000, p. 534-542.

Research output: Contribution to journalArticle

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