4N9V

High resolution x-ray structure of urate oxidase in complex with 8-azaxanthine

Summary for 4N9V

• Entry DOI: 10.2210/pdb4n9v/pdb
• Related: 2IBA 4N3M 4N9M 4N9S
• Descriptor: Uricase, 8-AZAXANTHINE, SODIUM ION, ... (7 entities in total)
• Functional Keywords: urate oxidase, uricase, oxidoreductase
• Biological source: Aspergillus flavus
• Cellular location: Peroxisome: Q00511
• Total number of polymer chains: 1
• Total formula weight: 34924.24

Authors

Oksanen, E.,Blakeley, M.P.,Budayova-Spano, M. (deposition date: 2013-10-21, release date: 2014-02-05, Last modification date: 2024-11-06)

Primary citation

Oksanen, E.,Blakeley, M.P.,El-Hajji, M.,Ryde, U.,Budayova-Spano, M.
The neutron structure of urate oxidase resolves a long-standing mechanistic conundrum and reveals unexpected changes in protonation.
Plos One, 9:e86651-e86651, 2014

PubMed Abstract: Urate oxidase transforms uric acid to 5-hydroxyisourate without the help of cofactors, but the catalytic mechanism has remained enigmatic, as the protonation state of the substrate could not be reliably deduced. We have determined the neutron structure of urate oxidase, providing unique information on the proton positions. A neutron crystal structure inhibited by a chloride anion at 2.3 Å resolution shows that the substrate is in fact 8-hydroxyxanthine, the enol tautomer of urate. We have also determined the neutron structure of the complex with the inhibitor 8-azaxanthine at 1.9 Å resolution, showing the protonation states of the K10-T57-H256 catalytic triad. Together with X-ray data and quantum chemical calculations, these structures allow us to identify the site of the initial substrate protonation and elucidate why the enzyme is inhibited by a chloride anion.

PubMed: 24466188
DOI: 10.1371/journal.pone.0086651

Experimental method

X-RAY DIFFRACTION (1.1 Å)