Vitamin B (cobalamin or Cbl) functions as a cofactor in two important enzymatic processes in human cells, and life is not sustainable without it. B is obtained from food and travels from the stomach, through the intestine, and into the bloodstream by three B-transporting proteins: salivary haptocorrin (HC), gastric intrinsic factor, and transcobalamin (TC), which all bind B with high affinity and require proteolytic degradation to liberate Cbl. After intracellular delivery of dietary B, Cbl in the aquo/hydroxocobalamin form can coordinate various nucleophiles, for example, GSH, giving rise to glutathionylcobalamin (GSCbl), a naturally occurring form of vitamin B. Currently, there is no data showing whether GSCbl is recognized and transported in the human body. Our crystallographic data shows for the first time the complex between a vitamin B transporter and GSCbl, which compared to aquo/hydroxocobalamin, binds TC equally well. Furthermore, sequence analysis and structural comparisons show that TC recognizes and transports GSCbl and that the residues involved are conserved among TCs from different organisms. Interestingly, haptocorrin and intrinsic factor are not structurally tailored to bind GSCbl. This study provides new insights into the interactions between TC and Cbl.

中文翻译：

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大鼠维生素B12转运蛋白TC及其与谷胱甘肽钴胺素复合物的结构


维生素 B（钴胺素或 Cbl）作为人体细胞中两个重要酶促过程的辅助因子，没有它，生命就无法持续。 B 是从食物中获得的，通过三种 B 转运蛋白：唾液结合蛋白 (HC)、胃内因子和转钴胺素 (TC) 从胃中穿过肠道进入血液，它们都以高亲和力与 B 结合，并且需要蛋白水解降解来释放 Cbl。在细胞内输送膳食 B 后，水合/羟钴胺形式的 Cbl 可以协调各种亲核试剂，例如 GSH，产生谷胱甘肽钴胺素 (GSCbl)，这是一种天然存在的维生素 B 形式。目前，没有数据表明 GSCbl 是否是在人体内被识别和运输。我们的晶体学数据首次显示维生素 B 转运蛋白和 GSCbl 之间的复合物，与水/羟钴胺相比，它与 TC 的结合同样好。此外，序列分析和结构比较表明TC识别并转运GSCbl，并且所涉及的残基在来自不同生物体的TC之间是保守的。有趣的是，haptocorrin 和内因子在结构上并不是为了结合 GSCbl 而定制的。这项研究为 TC 和 Cbl 之间的相互作用提供了新的见解。