5ll1: Difference between revisions
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==Crystal structure of urate oxidase from zebrafish== | ==Crystal structure of urate oxidase from zebrafish== | ||
<StructureSection load='5ll1' size='340' side='right' caption='[[5ll1]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='5ll1' size='340' side='right'caption='[[5ll1]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ll1]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LL1 OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5ll1]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LL1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LL1 FirstGlance]. <br> | ||
</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Factor_independent_urate_hydroxylase Factor independent urate hydroxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.7.3.3 1.7.3.3] </span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">uox ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Factor_independent_urate_hydroxylase Factor independent urate hydroxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.7.3.3 1.7.3.3] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ll1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ll1 OCA], [http://pdbe.org/5ll1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ll1 RCSB], [http://www.ebi.ac.uk/pdbsum/5ll1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ll1 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5ll1" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5ll1" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Urate Oxidase|Urate Oxidase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Brachidanio rerio]] | |||
[[Category: Factor independent urate hydroxylase]] | [[Category: Factor independent urate hydroxylase]] | ||
[[Category: Large Structures]] | |||
[[Category: Berni, R]] | [[Category: Berni, R]] | ||
[[Category: Cendron, l]] | [[Category: Cendron, l]] | ||
Revision as of 13:41, 12 August 2020
Crystal structure of urate oxidase from zebrafishCrystal structure of urate oxidase from zebrafish
Structural highlights
Function[Q6DG85_DANRE] Catalyzes the oxidation of uric acid to 5-hydroxyisourate, which is further processed to form (S)-allantoin.[PIRNR:PIRNR000241] Publication Abstract from PubMedUrate 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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