The hunt for 8-oxoguanine deaminase

J Am Chem Soc. 2010 Feb 17;132(6):1762-3. doi: 10.1021/ja909817d.


An enzyme from Pseudomonas aeruginosa, Pa0142 (gi|9945972), that is able to catalyze the deamination of 8-oxoguanine (8-oxoG) to uric acid has been identified for the first time. 8-Oxoguanine is formed by the oxidation of guanine residues within DNA by reactive oxygen species, and this lesion results in G:C to T:A transversions. The value of k(cat)/K(m) for the deamination of 8-oxoG by Pa0142 at pH 8.0 and 30 degrees C is 2.0 x 10(4) M(-1) s(-1). This enzyme can also catalyze the deamination of isocystosine and guanine at rates that are approximately an order of magnitude lower. The three-dimensional structure of a homologous enzyme (gi|44264246) from the Sargasso Sea has been determined by X-ray diffraction methods to a resolution of 2.2 A (PDB entry). The enzyme folds as a (beta/alpha)(8) barrel and is a member of the amidohydrolase superfamily with a single zinc in the active site. This enzyme catalyzes the deamination of 8-oxoG with a k(cat)/K(m) value of 2.7 x 10(5) M(-1) s(-1). Computational docking of potential high-energy intermediates for the deamination reaction to the X-ray crystal structure suggests that active-site binding of 8-oxoG is facilitated by hydrogen-bond interactions from a conserved glutamine that follows beta-strand 1 with the carbonyl group at C6, a conserved tyrosine that follows beta-strand 2 with N7, and a conserved cysteine residue that follows beta-strand 4 with the carbonyl group at C8. A bioinformatic analysis of available protein sequences suggests that approximately 200 other bacteria possess an enzyme capable of catalyzing the deamination of 8-oxoG.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Catalytic Domain
  • Cloning, Molecular
  • Escherichia coli / enzymology
  • Guanine / analogs & derivatives*
  • Guanine / metabolism
  • Guanine Deaminase / chemistry*
  • Guanine Deaminase / genetics
  • Guanine Deaminase / isolation & purification
  • Guanine Deaminase / metabolism*
  • Humans
  • Models, Molecular
  • Pseudomonas aeruginosa / enzymology
  • Uric Acid / metabolism


  • Uric Acid
  • 8-hydroxyguanine
  • Guanine
  • Guanine Deaminase