8z7y

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Current revision (07:57, 9 January 2025) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 8z7y is ON HOLD until 2026-04-21
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==SLC19A3-Fedratinib inward structure==
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<StructureSection load='8z7y' size='340' side='right'caption='[[8z7y]], [[Resolution|resolution]] 3.02&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8z7y]] 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=8Z7Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8Z7Y FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.02&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2TA:N-TERT-BUTYL-3-{[5-METHYL-2-({4-[2-(PYRROLIDIN-1-YL)ETHOXY]PHENYL}AMINO)PYRIMIDIN-4-YL]AMINO}BENZENESULFONAMIDE'>2TA</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8z7y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8z7y OCA], [https://pdbe.org/8z7y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8z7y RCSB], [https://www.ebi.ac.uk/pdbsum/8z7y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8z7y ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/S19A3_HUMAN S19A3_HUMAN] Thiamine-responsive encephalopathy;Biotin-thiamine-responsive basal ganglia disease;Infantile spasms-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome. The disease is caused by variants affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/S19A3_HUMAN S19A3_HUMAN] Mediates high affinity thiamine uptake, probably via a proton anti-port mechanism (PubMed:11731220, PubMed:33008889, PubMed:35512554, PubMed:35724964). Has no folate transport activity (PubMed:11731220). Mediates H(+)-dependent pyridoxine transport (PubMed:33008889, PubMed:35512554, PubMed:35724964, PubMed:36456177).<ref>PMID:11731220</ref> <ref>PMID:33008889</ref> <ref>PMID:35512554</ref> <ref>PMID:35724964</ref> <ref>PMID:36456177</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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Authors:
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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>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 8z7y" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Gao P]]
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[[Category: Li PP]]
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[[Category: Qu QH]]
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[[Category: Wang Y]]
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[[Category: Zhu ZN]]

Current revision

SLC19A3-Fedratinib inward structure

PDB ID 8z7y

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