View source for 8uvi


==Structure of NaDC3-Succinate complex in Coo-Coo conformation==
<StructureSection load='8uvi' size='340' side='right'caption='[[8uvi]], [[Resolution|resolution]] 2.53&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8uvi]] is a 2 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=8UVI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UVI 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]] 2.53&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C14:TETRADECANE'>C14</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</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=8uvi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8uvi OCA], [https://pdbe.org/8uvi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8uvi RCSB], [https://www.ebi.ac.uk/pdbsum/8uvi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8uvi ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/S13A3_HUMAN S13A3_HUMAN] The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/S13A3_HUMAN S13A3_HUMAN] High-affinity sodium-dicarboxylate cotransporter that accepts a range of substrates with 4-6 carbon atoms, such as the citric acid cycle intermediates succinate and alpha-ketoglutarate (2-oxoglutarate), as well as other compounds including N-acetyl-L-aspartate (PubMed:10794676, PubMed:10992006, PubMed:15561973, PubMed:17356845, PubMed:17426067, PubMed:24247155, PubMed:30635937). Transports the dicarboxylate into the cell with a probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate, rendering the process electrogenic (PubMed:10794676, PubMed:10992006). Can transport citrate in a Na(+)-dependent manner, recognizing the divalent form of citrate rather than the trivalent form which is normally found in blood (PubMed:10794676).<ref>PMID:10794676</ref> <ref>PMID:10992006</ref> <ref>PMID:15561973</ref> <ref>PMID:17356845</ref> <ref>PMID:17426067</ref> <ref>PMID:24247155</ref> <ref>PMID:30635937</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The human high-affinity sodium-dicarboxylate cotransporter (NaDC3) imports various substrates into the cell as tricarboxylate acid cycle intermediates, lipid biosynthesis precursors and signaling molecules. Understanding the cellular signaling process and developing inhibitors require knowledge of the structural basis of the dicarboxylate specificity and inhibition mechanism of NaDC3. To this end, we determined the cryo-electron microscopy structures of NaDC3 in various dimers, revealing the protomer in three conformations: outward-open C(o), outward-occluded C(oo) and inward-open C(i). A dicarboxylate is first bound and recognized in C(o) and how the substrate interacts with NaDC3 in C(oo) likely helps to further determine the substrate specificity. A phenylalanine from the scaffold domain interacts with the bound dicarboxylate in the C(oo) state and modulates the kinetic barrier to the transport domain movement. Structural comparison of an inhibitor-bound structure of NaDC3 to that of the sodium-dependent citrate transporter suggests ways for making an inhibitor that is specific for NaDC3.

Substrate translocation and inhibition in human dicarboxylate transporter NaDC3.,Li Y, Song J, Mikusevic V, Marden JJ, Becerril A, Kuang H, Wang B, Rice WJ, Mindell JA, Wang DN Nat Struct Mol Biol. 2024 Dec 2. doi: 10.1038/s41594-024-01433-0. PMID:39622972<ref>PMID:39622972</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8uvi" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Becerril A]]
[[Category: Kuang H]]
[[Category: Li Y]]
[[Category: Marden JJ]]
[[Category: Mikusevic V]]
[[Category: Mindell JA]]
[[Category: Rice WJ]]
[[Category: Song J]]
[[Category: Wang B]]
[[Category: Wang DN]]