J Michael Sauder - The hunt for 8-oxoguanine deaminase

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  Publication Details (including relevant citation   information):

  J Am Chem Soc (2010) 132: 1762-1763.

  Hall RS, Fedorov AA, Marti-Arbona R, Fedorov EV, Kolb P, Sauder   JM, Burley SK, Shoichet BK, Almo SC, Raushel FM

  Abstract:

  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.

  Address (URL): http://www.ncbi.nlm.nih.gov/pubmed/20088583

 

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