View source for 5m98


==Crystal structure of urate oxidase from zebrafish==
<StructureSection load='5m98' size='340' side='right'caption='[[5m98]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5m98]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M98 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5M98 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]] 2.8&#8491;</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=5m98 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m98 OCA], [https://pdbe.org/5m98 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5m98 RCSB], [https://www.ebi.ac.uk/pdbsum/5m98 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5m98 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/URIC_DANRE URIC_DANRE] Catalyzes the oxidation of uric acid to 5-hydroxyisourate, which is further processed to form (S)-allantoin.[PIRNR:PIRNR000241][RuleBase:RU004455]<ref>PMID:27922051</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Urate oxidase (Uox) catalyses the first reaction of oxidative uricolysis, a three-step enzymatic pathway that allows some animals to eliminate purine nitrogen through a water-soluble compound. Inactivation of the pathway in hominoids leads to elevated levels of sparingly soluble urate and puts humans at risk of hyperuricemia and gout. The uricolytic activities lost during evolution can be replaced by enzyme therapy. Here we report on the functional and structural characterization of Uox from zebrafish and the effects on the enzyme of the missense mutation (F216S) that preceded Uox pseudogenization in hominoids. Using a kinetic assay based on the enzymatic suppression of the spectroscopic interference of the Uox reaction product, we found that the F216S mutant has the same turnover number of the wild-type enzyme but a much-reduced affinity for the urate substrate and xanthine inhibitor. Our results indicate that the last functioning Uox in hominoid evolution had an increased Michaelis constant, possibly near to upper end of the normal range of urate in the human serum (~300 muM). Changes in the renal handling of urate during primate evolution can explain the genetic modification of uricolytic activities in the hominoid lineage without the need of assuming fixation of deleterious mutations.

Catalysis and Structure of Zebrafish Urate Oxidase Provide Insights into the Origin of Hyperuricemia in Hominoids.,Marchetti M, Liuzzi A, Fermi B, Corsini R, Folli C, Speranzini V, Gandolfi F, Bettati S, Ronda L, Cendron L, Berni R, Zanotti G, Percudani R Sci Rep. 2016 Dec 6;6:38302. doi: 10.1038/srep38302. PMID:27922051<ref>PMID:27922051</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5m98" style="background-color:#fffaf0;"></div>

==See Also==
*[[Urate oxidase 3D structures|Urate oxidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Danio rerio]]
[[Category: Large Structures]]
[[Category: Berni R]]
[[Category: Cendron l]]
[[Category: Percudani R]]
[[Category: Zanotti G]]