3L8W

Urate oxidase from aspergillus flavus complexed with xanthin

Summary for 3L8W

• Entry DOI: 10.2210/pdb3l8w/pdb
• Related: 1R4S 1R4U 1R51 1R56 1WRR 1XT4 3L9G 3LBG
• Descriptor: Uricase, XANTHINE, SODIUM ION, ... (5 entities in total)
• Functional Keywords: oxidoreductase, uric acid degradation, xanthine, inhibition aspergillus flavus, peroxisome, purine metabolism
• Biological source: Aspergillus flavus
• Cellular location: Peroxisome: Q00511
• Total number of polymer chains: 1
• Total formula weight: 33894.09

Authors

Prange, T.,Gabison, L.,Colloc'h, N.,Chiadmi, M. (deposition date: 2010-01-04, release date: 2010-06-02, Last modification date: 2024-11-13)

Primary citation

Gabison, L.,Chiadmi, M.,El Hajji, M.,Castro, B.,Colloc'h, N.,Prange, T.
Near-atomic resolution structures of urate oxidase complexed with its substrate and analogues: the protonation state of the ligand.
Acta Crystallogr.,Sect.D, 66:714-724, 2010

PubMed Abstract: Urate oxidase (uricase; EC 1.7.3.3; UOX) from Aspergillus flavus catalyzes the oxidation of uric acid in the presence of molecular oxygen to 5-hydroxyisourate in the degradation cascade of purines; intriguingly, catalysis proceeds using neither a metal ion (Fe, Cu etc.) nor a redox cofactor. UOX is a tetrameric enzyme with four active sites located at the interface of two subunits; its structure was refined at atomic resolution (1 A) using new crystal data in the presence of xanthine and at near-atomic resolution (1.3-1.7 A) in complexes with the natural substrate (urate) and two inhibitors: 8-nitroxanthine and 8-thiouric acid. Three new features of the structural and mechanistic behaviour of the enzyme were addressed. Firstly, the high resolution of the UOX-xanthine structure allowed the solution of an old structural problem at a contact zone within the tetramer; secondly, the protonation state of the substrate was determined from both a halochromic inhibitor complex (UOX-8-nitroxanthine) and from the H-atom distribution in the active site, using the structures of the UOX-xanthine and the UOX-uric acid complexes; and thirdly, it was possible to extend the general base system, characterized by the conserved catalytic triad Thr-Lys-His, to a large water network that is able to buffer and shuttle protons back and forth between the substrate and the peroxo hole along the reaction pathway.

PubMed: 20516624
DOI: 10.1107/S090744491001142X

Experimental method

X-RAY DIFFRACTION (1 Å)