View source for 8wjq


==Cryo-EM structure of human protein C==
<StructureSection load='8wjq' size='340' side='right'caption='[[8wjq]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8wjq]] 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=8WJQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8WJQ 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]] 3.8&#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=8wjq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8wjq OCA], [https://pdbe.org/8wjq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8wjq RCSB], [https://www.ebi.ac.uk/pdbsum/8wjq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8wjq ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/S22AC_HUMAN S22AC_HUMAN] Hereditary renal hypouricemia. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/S22AC_HUMAN S22AC_HUMAN] Electroneutral antiporter that translocates urate across the apical membrane of proximal tubular cells in exchange for monovalent organic or inorganic anions (PubMed:12024214, PubMed:22194875, PubMed:35144162, PubMed:35462902). Involved in renal reabsorption of urate and helps maintaining blood levels of uric acid (PubMed:12024214, PubMed:22194875). Mediates urate uptake by an exchange with organic anions such as (S)-lactate and nicotinate, and inorganic anion Cl(-) (PubMed:12024214). Other inorganic anions such as Br(-), I(-) and NO3(-) may also act as counteranions that exchange for urate (PubMed:12024214). Also mediates orotate tubular uptake coupled with nicotinate efflux and to a lesser extent with lactate efflux, therefore displaying a potential role in orotate renal reabsorption (PubMed:21350910). Orotate transport is Cl(-)-dependent (PubMed:21350910).<ref>PMID:12024214</ref> <ref>PMID:21350910</ref> <ref>PMID:22194875</ref> <ref>PMID:35144162</ref> <ref>PMID:35462902</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
High serum urate levels are the major risk factor for gout. URAT1, the primary transporter for urate absorption in the kidneys, is well known as an anti-hyperuricemia drug target. However, the clinical application of URAT1-targeted drugs is limited because of their low specificity and severe side effects. The lack of structural information impedes elucidation of the transport mechanism and the development of new drugs. Here, we present the cryoelectron microscopy (cryo-EM) structures of human URAT1(R477S), its complex with urate, and its closely related homolog OAT4. URAT1(R477S) and OAT4 exhibit major facilitator superfamily (MFS) folds with outward- and inward-open conformations, respectively. Structural comparison reveals a 30 degrees rotation between the N-terminal and C-terminal domains, supporting an alternating access mechanism. A conserved arginine (OAT4-Arg473/URAT1-Arg477) is found to be essential for chloride-mediated inhibition. The URAT1(R477S)-urate complex reveals the specificity of urate recognition. Taken together, our study promotes our understanding of the transport mechanism and substrate selection of URAT1.

Structural basis for the transport and substrate selection of human urate transporter 1.,He J, Liu G, Kong F, Tan Q, Wang Z, Yang M, He Y, Jia X, Yan C, Wang C, Qian H Cell Rep. 2024 Aug 14;43(8):114628. doi: 10.1016/j.celrep.2024.114628. PMID:39146184<ref>PMID:39146184</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8wjq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: He JJ]]
[[Category: Qian HW]]