Crystal Structure of Urate Oxidase from Bacillus Subtilis 168

Urate oxidase catalyzes the oxidative degradation of uric acid to allantoin via peroxide formation by a radical recombination mechanism. Here the crystal structure of urate oxidase (residues 4-310) from Bacillus subtilis 168 ( Bs UOX) was solved at 2.6 Å resolution. Both crystal structure and small angle X-ray scattering data confirmed that the Bs UOX adopts a tetrameric conformation. Comparative analysis of Bs UOX structure alignment with crystal structure of urate oxidase complexed with uric acid from Aspergillus flavus (PDB entry 4D12) showed some conserved Bs UOX amino acid residues, Thr69, Ser243, Gln245, and Asn271, in the active site region that can potentially bind uric acid. Residues Ile244 and Gln299 are also predicted to interact with the uric acid via hydrophobic interactions but needs further confirmation. This work will be helpful for further functional and biochemical studies of the enzyme for future drug design and development against gout and hyperuricemia.