3PKH

Urate oxidase under 1.5 MPa / 15 bars pressure of xenon

Summary for 3PKH

• Entry DOI: 10.2210/pdb3pkh/pdb
• Related: 2IBA 2IC0 2ICQ 3PJK 3PK3 3PK4 3PK5 3PK6 3PK8 3PKF 3PKG 3PKK 3PKL 3PKS 3PKT 3PKU 3PLE 3PLG 3PLH 3PLI 3PLJ 3PLM
• Descriptor: Uricase, 8-AZAXANTHINE, SODIUM ION, ... (5 entities in total)
• Functional Keywords: t-fold, oxidase, peroxisome, tetramer, uric acid degradation, oxidoreductase
• Biological source: Aspergillus flavus
• Cellular location: Peroxisome: Q00511
• Total number of polymer chains: 1
• Total formula weight: 34622.26

Authors

Marassio, G.,Colloc'h, N.,Prange, T.,Abraini, J.H. (deposition date: 2010-11-11, release date: 2011-04-06, Last modification date: 2023-09-06)

Primary citation

Marassio, G.,Prange, T.,David, H.N.,Sopkova-de Oliveira Santos, J.,Gabison, L.,Delcroix, N.,Abraini, J.H.,Colloc'h, N.
Pressure-response analysis of anesthetic gases xenon and nitrous oxide on urate oxidase: a crystallographic study.
Faseb J., 25:2266-2275, 2011

PubMed Abstract: The remarkably safe anesthetics xenon (Xe) and, to lesser extent, nitrous oxide (N(2)O) possess neuroprotective properties in preclinical studies. To investigate the mechanisms of pharmacological action of these gases, which are still poorly known, we performed both crystallography under a large range of gas pressure and biochemical studies on urate oxidase, a prototype of globular gas-binding proteins whose activity is modulated by inert gases. We show that Xe and N(2)O bind to, compete for, and expand the volume of a hydrophobic cavity located just behind the active site of urate oxidase and further inhibit urate oxidase enzymatic activity. By demonstrating a significant relationship between the binding and biochemical effects of Xe and N(2)O, given alone or in combination, these data from structure to function highlight the mechanisms by which chemically and metabolically inert gases can alter protein function and produce their pharmacological effects. Interestingly, the effects of a Xe:N(2)O equimolar mixture were found to be equivalent to those of Xe alone, thereby suggesting that gas mixtures containing Xe and N(2)O could be an alternative and efficient neuroprotective strategy to Xe alone, whose widespread clinical use is limited due to the cost of production and availability of this gas.

PubMed: 21421845
DOI: 10.1096/fj.11-183046

Experimental method

X-RAY DIFFRACTION (1.71 Å)