The hunt for 8-oxoguanine deaminase

Richard S. Hall, Alexander A. Fedorov, Ricardo Marti-Arbona, Elena V. Fedorov, Peter Kolb, J. Michael Sauder, Stephen K. Burley, Brian K. Shoichet, Steven C. Almo, Frank M. Raushel

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

(Chemical Equation Presented) 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/Km for the deamination of 8-oxoG by Pa0142 at pH 8.0 and 30 ° C is 2.0 × 104 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 Å (PDB entry ). The enzyme folds as a (β/α)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 kcat/K m value of 2.7 × 105 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 β-strand 1 with the carbonyl group at C6, a conserved tyrosine that follows β-strand 2 with N7, and a conserved cysteine residue that follows β-strand 4 with the carbonyl group at C8. A bioinformatic analysis of available protein sequences suggests that ∼200 other bacteria possess an enzyme capable of catalyzing the deamination of 8-oxoG.

Original languageEnglish (US)
Pages (from-to)1762-1763
Number of pages2
JournalJournal of the American Chemical Society
Volume132
Issue number6
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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