Publication Details (including relevant citation information):
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. Journal of the American Chemical Society (2010), 132(6), 1762-1763. ISSN: 0002-7863. 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 kcat/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/Km 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.
Address (URL): http://pubs.acs.org/doi/full/10.1021/ja909817d