View source for 8z80


==SLC19A2-Pyridoxine inward structure==
<StructureSection load='8z80' size='340' side='right'caption='[[8z80]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8z80]] 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=8Z80 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8Z80 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]] 3.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UEG:4,5-BIS(HYDROXYMETHYL)-2-METHYL-PYRIDIN-3-OL'>UEG</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=8z80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8z80 OCA], [https://pdbe.org/8z80 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8z80 RCSB], [https://www.ebi.ac.uk/pdbsum/8z80 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8z80 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/S19A2_HUMAN S19A2_HUMAN] Thiamine-responsive megaloblastic anemia syndrome. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/S19A2_HUMAN S19A2_HUMAN] High-affinity transporter for the intake of thiamine (PubMed:10391222, PubMed:10542220, PubMed:21836059, PubMed:33008889, PubMed:35512554, PubMed:35724964). Mediates H(+)-dependent pyridoxine transport (PubMed:33008889, PubMed:35512554, PubMed:35724964).<ref>PMID:10391222</ref> <ref>PMID:10542220</ref> <ref>PMID:21836059</ref> <ref>PMID:33008889</ref> <ref>PMID:35512554</ref> <ref>PMID:35724964</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Thiamine and pyridoxine are essential B vitamins that serve as enzymatic cofactors in energy metabolism, protein and nucleic acid biosynthesis, and neurotransmitter production. In humans, thiamine transporters SLC19A2 and SLC19A3 primarily regulate cellular uptake of both vitamins. Genetic mutations in these transporters, which cause thiamine and pyridoxine deficiency, have been implicated in severe neurometabolic diseases. Additionally, various prescribed medicines, including metformin and fedratinib, manipulate thiamine transporters, complicating the therapeutic effect. Despite their physiological and pharmacological significance, the molecular underpinnings of substrate and drug recognition remain unknown. Here we present ten cryo-EM structures of human thiamine transporters SLC19A3 and SLC19A2 in outward- and inward-facing conformations, complexed with thiamine, pyridoxine, metformin, fedratinib, and amprolium. These structural insights, combined with functional characterizations, illuminate the translocation mechanism of diverse chemical entities, and enhance our understanding of drug-nutrient interactions mediated by thiamine transporters.

Substrate transport and drug interaction of human thiamine transporters SLC19A2/A3.,Li P, Zhu Z, Wang Y, Zhang X, Yang C, Zhu Y, Zhou Z, Chao Y, Long Y, Gao Y, Liu S, Zhang L, Gao P, Qu Q Nat Commun. 2024 Dec 30;15(1):10924. doi: 10.1038/s41467-024-55359-8. PMID:39738067<ref>PMID:39738067</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8z80" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gao P]]
[[Category: Li PP]]
[[Category: Qu QH]]
[[Category: Wang Y]]
[[Category: Zhu ZN]]