View source for 8zxm


==Cryo-EM structure of human GLUT9 bound to urate==
<StructureSection load='8zxm' size='340' side='right'caption='[[8zxm]], [[Resolution|resolution]] 3.39&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8zxm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ZXM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZXM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.39&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=URC:URIC+ACID'>URC</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=8zxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8zxm OCA], [https://pdbe.org/8zxm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8zxm RCSB], [https://www.ebi.ac.uk/pdbsum/8zxm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8zxm ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GTR9_HUMAN GTR9_HUMAN] Hereditary renal hypouricemia. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/GTR9_HUMAN GTR9_HUMAN] High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules (PubMed:18327257, PubMed:18701466, PubMed:22647630, PubMed:28083649, PubMed:36749388). May have a residual high-affinity, low-capacity glucose and fructose transporter activity (PubMed:18327257, PubMed:18701466, PubMed:18842065). Transports urate at rates 45- to 60-fold faster than glucose (PubMed:18842065). Does not transport galactose (PubMed:28083649). May mediate small uptake of adenine but not of other nucleobases (PubMed:22647630).<ref>PMID:18327257</ref> <ref>PMID:18701466</ref> <ref>PMID:18842065</ref> <ref>PMID:22647630</ref> <ref>PMID:28083649</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glucose transporter 9 (GLUT9) is a critical urate transporter involved in renal reabsorption, playing a pivotal role in regulating physiological urate levels and representing a potential therapeutic target for gout. Despite such clinical significance, the structural basis of urate recognition and transport by GLUT9 remains elusive. Here, we present the cryoelectron microscopy (cryo-EM) structures of GLUT9 in the inward-open conformation in both apo and urate-bound states. Urate binds in a cleft between the N-terminal and C-terminal domains, interacting via hydrogen bonds and hydrophobic interactions. Structural comparison with sugar-transporting GLUTs highlights unique amino acid compositions in the substrate recognition pocket of GLUT9. Functional and mutational studies directly measuring GLUT9-mediated urate uptake further demonstrate the cooperative roles of multiple residues in urate recognition. Our findings elucidate the structural basis of urate transport by GLUT9 and provide valuable insights for the development of uricosuric drugs targeting GLUT9.

Structural basis of urate transport by glucose transporter 9.,Matsushita D, Toyoda Y, Lee Y, Aoi M, Matsuo H, Takada T, Nishizawa T Cell Rep. 2025 Apr 4;44(4):115514. doi: 10.1016/j.celrep.2025.115514. PMID:40186864<ref>PMID:40186864</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8zxm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Lee Y]]
[[Category: Matsushita D]]
[[Category: Nishizawa T]]