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 Citations (Scopus)

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

Fingerprint

Deamination
Enzymes
Guanine
Catalytic Domain
Amidohydrolases
Protein Sequence Analysis
Binding sites
Bioinformatics
Uric Acid
Computational Biology
Glutamine
X-Ray Diffraction
Oceans and Seas
Pseudomonas aeruginosa
Cysteine
Tyrosine
8-hydroxyguanine
Zinc
Hydrogen
Reactive Oxygen Species

ASJC Scopus subject areas

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

Cite this

Hall, R. S., Fedorov, A. A., Marti-Arbona, R., Fedorov, E. V., Kolb, P., Sauder, J. M., ... Raushel, F. M. (2010). The hunt for 8-oxoguanine deaminase. Journal of the American Chemical Society, 132(6), 1762-1763. https://doi.org/10.1021/ja909817d

The hunt for 8-oxoguanine deaminase. / Hall, Richard S.; Fedorov, Alexander A.; Marti-Arbona, Ricardo; Fedorov, Elena V.; Kolb, Peter; Sauder, J. Michael; Burley, Stephen K.; Shoichet, Brian K.; Almo, Steven C.; Raushel, Frank M.

In: Journal of the American Chemical Society, Vol. 132, No. 6, 2010, p. 1762-1763.

Research output: Contribution to journalArticle

Hall, RS, Fedorov, AA, Marti-Arbona, R, Fedorov, EV, Kolb, P, Sauder, JM, Burley, SK, Shoichet, BK, Almo, SC & Raushel, FM 2010, 'The hunt for 8-oxoguanine deaminase', Journal of the American Chemical Society, vol. 132, no. 6, pp. 1762-1763. https://doi.org/10.1021/ja909817d
Hall RS, Fedorov AA, Marti-Arbona R, Fedorov EV, Kolb P, Sauder JM et al. The hunt for 8-oxoguanine deaminase. Journal of the American Chemical Society. 2010;132(6):1762-1763. https://doi.org/10.1021/ja909817d
Hall, Richard S. ; Fedorov, Alexander A. ; Marti-Arbona, Ricardo ; Fedorov, Elena V. ; Kolb, Peter ; Sauder, J. Michael ; Burley, Stephen K. ; Shoichet, Brian K. ; Almo, Steven C. ; Raushel, Frank M. / The hunt for 8-oxoguanine deaminase. In: Journal of the American Chemical Society. 2010 ; Vol. 132, No. 6. pp. 1762-1763.
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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 {\AA} (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.",
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