Urate Oxidase: Difference between revisions

The complete functional structure of urate oxidase is a 135-kDa barrel-shaped homo-tetramer that has a height of 7 nm, with an inner radius of 0.6 nm and an outer radius of 3 nm.  It has four identical active sites that are found at dimeric interfaces formed between the monomers and a central void tunnel of unknown function that is 5 nm long and has a diameter of 1.2 nm.  Each monomer, formed by 301 amino acid residues, has two structurally equivalent domains, which Collac`h ''et al.'' termed ``tunneling fold`` domains (this feature allows urate oxidase to be placed in the expanding family of tunnel-shaped proteins that also includes 3i2b and 1a9c). These domains are comprised of a four-strand long antiparallel beta sheet with two helices on the concave side.  Together, the two tunneling fold domains of each monomer form an eight-strand long antiparallel beta sheet, where all four helices are found on the concave side of the sheet.  The dimer forms an α₈β₁₆ barrel, in which the eight helices make up the outer surface of the barrel.

Within the active site two residues, Arg 176 and Gln 228, are responsible for hydrogen-binding the substrate (uric acid).  Approximately 0.33 nm above the ligand, Asn 254 and Thr 57* (* indicates a residue from a different symmetric subunit), hydrogen-bond the catalytic water molecule.  The catalytic water molecule and the γ oxygen of Thr 57* are the beginning of a proton transfer chain that also involves Lys 10*, His 256 and two other water molceules, ending at N9 of uric acid.