EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Substrate transport and drug interaction of human thiamine transporters SLC19A2/A3.
ジャーナル・号・ページ	Nat Commun, Vol. 15, Issue 1, Page 10924, Year 2024
掲載日	2024年12月30日
著者	Peipei Li / Zhini Zhu / Yong Wang / Xuyuan Zhang / Chuanhui Yang / Yalan Zhu / Zixuan Zhou / Yulin Chao / Yonghui Long / Yina Gao / Songqing Liu / Liguo Zhang / Pu Gao / Qianhui Qu /
PubMed 要旨	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 ...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.
リンク	Nat Commun / PubMed:39738067 / PubMed Central
手法	EM (単粒子)
解像度	3.02 - 3.7 Å
構造データ	39825 8z7r EMDB-39825, PDB-8z7r: SLC19A3 apo structure 手法: EM (単粒子) / 解像度: 3.15 Å 39826 8z7s EMDB-39826, PDB-8z7s: SLC19A3-thiamine outward structure 手法: EM (単粒子) / 解像度: 3.05 Å 39827 8z7t EMDB-39827, PDB-8z7t: SLC19A3-Pyridoxine outward structure 手法: EM (単粒子) / 解像度: 3.39 Å 39828 8z7u EMDB-39828, PDB-8z7u: SLC19A3-Fedratinib outward structure 手法: EM (単粒子) / 解像度: 3.1 Å 39829 8z7v EMDB-39829, PDB-8z7v: Slc19A3-Amprolium outward structure 手法: EM (単粒子) / 解像度: 3.1 Å 39830 8z7w EMDB-39830, PDB-8z7w: SLC19A3-Metformin outward structure 手法: EM (単粒子) / 解像度: 3.09 Å 39831 8z7x EMDB-39831, PDB-8z7x: SLC19A3-Thiamine inward structure 手法: EM (単粒子) / 解像度: 3.36 Å 39832 8z7y EMDB-39832, PDB-8z7y: SLC19A3-Fedratinib inward structure 手法: EM (単粒子) / 解像度: 3.02 Å 39833 8z7z EMDB-39833, PDB-8z7z: SLC19A2-Thiamine inward structure 手法: EM (単粒子) / 解像度: 3.23 Å 39834 8z80 EMDB-39834, PDB-8z80: SLC19A2-Pyridoxine inward structure 手法: EM (単粒子) / 解像度: 3.7 Å
化合物	ChemComp-VIB: 3-(4-AMINO-2-METHYL-PYRIMIDIN-5-YLMETHYL)-5-(2-HYDROXY-ETHYL)-4-METHYL-THIAZOL-3-IUM / 薬剤YM ChemComp-UEG: 4,5-bis(hydroxymethyl)-2-methyl-pyridin-3-ol ChemComp-2TA: N-tert-butyl-3-{[5-methyl-2-({4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}amino)pyrimidin-4-yl]amino}benzenesulfonamide / 薬剤, 抗がん剤YM PDB-1h5c: X-ray induced reduction of horseradish peroxidase C1A Compound III (100-200% dose) ChemComp-MF8: Metformin / 薬剤, 抗精神病薬*YM
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN / Thiamine transporter / MFS