SLC19A3 的底物和药物识别机制

IF 28.1 1区 生物学 Q1 CELL BIOLOGY Cell Research Pub Date : 2024-03-19 DOI:10.1038/s41422-024-00951-2
Yu Dang, Tianyi Zhang, Shabareesh Pidathala, Guopeng Wang, Yijie Wang, Nanhao Chen, Chen Song, Chia-Hsueh Lee, Zhe Zhang
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摘要

亲爱的编辑,维生素B1和B6是两种水溶性维生素。它们的活性形式是焦磷酸硫胺素和 5′-磷酸吡哆醛,是参与多种生化反应的众多酶的辅助因子,对维持人体的组成和能量代谢至关重要1。因此,缺乏这两种维生素会导致多种疾病,如神经系统异常和心血管疾病2。迄今为止,已确定硫胺素转运体 1(ThTr1 或 SLC19A2)和硫胺素转运体 2(ThTr2 或 SLC19A3)这两种特异性转运体是参与摄取这两种维生素的主要跨膜转运体。有趣的是,用于治疗骨髓纤维化的临床抗肿瘤药物 fedratinib(一种 Janus 激酶 2(JAK2)抑制剂)在一些骨髓纤维化患者中会因硫胺素缺乏而诱发 Wernicke 脑病。9 在此,我们报告了人 SLC19A3 与维生素 B1、B6 或 fedratinib 复合物的冷冻电镜(cryo-EM)结构。值得注意的是,所有这些化合物都通过一个密切相关的结构元素与 SLC19A3 上的相同位点结合。突变研究进一步揭示了 SLC19A3 识别底物和药物的关键残基。总之,我们的工作为理解 SLC19A3 底物的多样性提供了一个结构框架。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Substrate and drug recognition mechanisms of SLC19A3
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来源期刊
Cell Research
Cell Research 生物-细胞生物学
CiteScore
53.90
自引率
0.70%
发文量
2420
审稿时长
2.3 months
期刊介绍: Cell Research (CR) is an international journal published by Springer Nature in partnership with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). It focuses on publishing original research articles and reviews in various areas of life sciences, particularly those related to molecular and cell biology. The journal covers a broad range of topics including cell growth, differentiation, and apoptosis; signal transduction; stem cell biology and development; chromatin, epigenetics, and transcription; RNA biology; structural and molecular biology; cancer biology and metabolism; immunity and molecular pathogenesis; molecular and cellular neuroscience; plant molecular and cell biology; and omics, system biology, and synthetic biology. CR is recognized as China's best international journal in life sciences and is part of Springer Nature's prestigious family of Molecular Cell Biology journals.
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