View source for 8ofk


==Crystal structure of the cysteine-rich Gallus gallus urate oxidase in complex with the 8-azaxanthine inhibitor under reducing conditions (space group C 2 2 21)==
<StructureSection load='8ofk' size='340' side='right'caption='[[8ofk]], [[Resolution|resolution]] 1.71&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ofk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8OFK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OFK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.713&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AZA:8-AZAXANTHINE'>AZA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=OXY:OXYGEN+MOLECULE'>OXY</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8ofk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ofk OCA], [https://pdbe.org/8ofk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ofk RCSB], [https://www.ebi.ac.uk/pdbsum/8ofk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ofk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A8V0ZED1_CHICK A0A8V0ZED1_CHICK] Catalyzes the oxidation of uric acid to 5-hydroxyisourate, which is further processed to form (S)-allantoin.[ARBA:ARBA00003860][PIRNR:PIRNR000241][RuleBase:RU004455]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Uric acid is the main means of nitrogen excretion in uricotelic vertebrates (birds and reptiles) and the end product of purine catabolism in humans and a few other mammals. While uricase is inactivated in mammals unable to degrade urate, the presence of orthologous genes without inactivating mutations in avian and reptilian genomes is unexplained. Here we show that the Gallus gallus gene we name cysteine-rich urate oxidase (CRUOX) encodes a functional protein representing a unique case of cysteine enrichment in the evolution of vertebrate orthologous genes. CRUOX retains the ability to catalyze urate oxidation to hydrogen peroxide and 5-hydroxyisourate (HIU), albeit with a 100-fold reduced efficiency. However, differently from all uricases hitherto characterized, it can also facilitate urate regeneration from HIU, a catalytic property that we propose depends on its enrichment in cysteine residues. X-ray structural analysis highlights differences in the active site compared to known orthologs and suggests a mechanism for cysteine-mediated self-aggregation under H2O2-oxidative conditions. Cysteine enrichment was concurrent with the transition to uricotelism and a shift in gene expression from the liver to the skin where CRUOX is co-expressed with beta-keratins. Therefore, the loss of urate degradation in amniotes has followed opposite evolutionary trajectories: while uricase has been eliminated by pseudogenization in some mammals, it has been repurposed as a redox-sensitive enzyme in the reptilian skin.

Cysteine Enrichment Mediates Co-Option of Uricase in Reptilian Skin and Transition to Uricotelism.,Mori G, Liuzzi A, Ronda L, Di Palma M, Chegkazi MS, Bui S, Garcia-Maya M, Ragazzini J, Malatesta M, Della Monica E, Rivetti C, Antin PB, Bettati S, Steiner RA, Percudani R Mol Biol Evol. 2023 Sep 1;40(9):msad200. doi: 10.1093/molbev/msad200. PMID:37695804<ref>PMID:37695804</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ofk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Gallus gallus]]
[[Category: Large Structures]]
[[Category: Bui S]]
[[Category: Chegkazi M]]
[[Category: Di Palma M]]
[[Category: Mori G]]
[[Category: Percudani R]]
[[Category: Steiner RA]]