4PR8: URATE OXIDASE AZIDE URIC ACID TERNARY complex

Citation:
Acta Crystallogr F Struct Biol Commun (2014) 70 p.896-902» All references (2)
Abstract
The inhibition of urate oxidase (UOX) by azide was investigated by X-ray diffraction techniques and compared with cyanide inhibition. Two well characterized sites for reagents are present in the enzyme: the dioxygen site and the substrate-binding site. To examine the selectivity of these sites towards azide inhibition, several crystallization conditions were developed. UOX was co-crystallized with azide (N3) in the presence or absence of either uric acid (UA, the natural substrate) or 8-azaxanthine (8AZA, a competitive inhibitor). In a second set of experiments, previously grown orthorhombic crystals of the UOX-UA or UOX-8AZA complexes were soaked in sodium azide solutions. In a third set of experiments, orthorhombic crystals of UOX with the exchangeable ligand 8-nitroxanthine (8NXN) were soaked in a solution containing uric acid and azide simultaneously (competitive soaking). In all assays, the soaking periods were either short (a few hours) or long (one or two months). These different experimental conditions showed that one or other of the sites, or the two sites together, could be inhibited. This also demonstrated that azide not only competes with dioxygen as cyanide does but also competes with the substrate for its enzymatic site. A model in agreement with experimental data would be an azide in equilibrium between two sites, kinetically in favour of the dioxygen site and thermodynamically in favour of the substrate-binding site.
PDB ID: 4PR8Download
MMDB ID: 146083
PDB Deposition Date: 2014/3/5
Updated in MMDB: 2016/12
Experimental Method:
x-ray diffraction
Resolution: 1.16  Å
Source Organism:
Similar Structures:
Biological Unit for 4PR8: tetrameric; determined by author and by software (PISA)
Molecular Components in 4PR8
Label Count Molecule
Proteins (4 molecules)
4
Uricase
Molecule annotation
Chemicals (16 molecules)
1
4
2
8
3
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.