3HPA

Crystal structure of an amidohydrolase gi:44264246 from an evironmental sample of sargasso sea

Replaces:  3H4U

Summary for 3HPA

• Entry DOI: 10.2210/pdb3hpa/pdb
• Related: 3H4U
• Descriptor: AMIDOHYDROLASE, ZINC ION (3 entities in total)
• Functional Keywords: amidohydrolase, signature of zn ligands, structural genomics, nysgxrc, target 9236e, psi-2, protein structure initiative, new york sgx research center for structural genomics, hydrolase
• Biological source: unidentified
• Total number of polymer chains: 2
• Total formula weight: 103802.49

Authors

Fedorov, A.A.,Fedorov, E.V.,Toro, R.,Raushel, F.M.,Burley, S.K.,Almo, S.C.,New York SGX Research Center for Structural Genomics (NYSGXRC) (deposition date: 2009-06-03, release date: 2009-06-16, Last modification date: 2024-02-21)

Primary citation

Hall, R.S.,Fedorov, A.A.,Marti-Arbona, R.,Fedorov, E.V.,Kolb, P.,Sauder, J.M.,Burley, S.K.,Shoichet, B.K.,Almo, S.C.,Raushel, F.M.
The hunt for 8-oxoguanine deaminase.
J.Am.Chem.Soc., 132:1762-1763, 2010

PubMed 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.

PubMed: 20088583
DOI: 10.1021/ja909817d

Experimental method

X-RAY DIFFRACTION (2.2 Å)