8Z7X

SLC19A3-Thiamine inward structure

8Z7X の概要

• エントリーDOI: 10.2210/pdb8z7x/pdb
• EMDBエントリー: 39831
• 分子名称: Thiamine transporter 2, 3-(4-AMINO-2-METHYL-PYRIMIDIN-5-YLMETHYL)-5-(2-HYDROXY-ETHYL)-4-METHYL-THIAZOL-3-IUM (2 entities in total)
• 機能のキーワード: thiamine transporter, mfs, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 55964.67

構造登録者

Li, P.P.,Zhu, Z.N.,Wang, Y.,Gao, P.,Qu, Q.H. (登録日: 2024-04-21, 公開日: 2025-01-08)

主引用文献

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.
Substrate transport and drug interaction of human thiamine transporters SLC19A2/A3.
Nat Commun, 15:10924-10924, 2024

PubMed Abstract: 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.

PubMed: 39738067
DOI: 10.1038/s41467-024-55359-8

実験手法

ELECTRON MICROSCOPY (3.36 Å)