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. 2022 Dec 28;8:141. doi: 10.1038/s41421-022-00508-w

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — SLC19A1 utilizes the alternating access mechanism to reverse transport two substrates. Under physiological conditions, 5-MTHF and TPP are likely the favorite extracellular and intracellular substrates of SLC19A1, respectively. They compete for the same binding site within the central cavity of SLC19A1. The four key residues (Glu123, Arg133, Tyr281, and Arg373) for substrate recognition are indicated.