Structural basis for promotion of duodenal iron absorption by enteric ferric reductase with ascorbate.
Structural basis for promotion of duodenal iron absorption by enteric ferric reductase with ascorbate.
复制标题
DOI：
10.1038/s42003-018-0121-8
复制
发表时间：
2018
影响因子：
5.9
通讯作者：
Sawai H
中科院分区：
文献类型：
--
作者：
Ganasen M;Togashi H;Takeda H;Asakura H;Tosha T;Yamashita K;Hirata K;Nariai Y;Urano T;Yuan X;Hamza I;Mauk AG;Shiro Y;Sugimoto H;Sawai H
膳食铁的吸收受十二指肠细胞色素b （Dcytb）的调节，Dcytb是一种完整的膜蛋白，通过抗坏血酸在膜上的电子转移催化非血红素Fe3+的还原。这一步骤对于二价金属转运体摄取铁至关重要。本文报道了人Dcytb及其与抗坏血酸和Zn2+复合物的晶体结构。同型二聚体蛋白的每个单体都具有细胞质和根尖血红素基团，以及位于每个血红素附近的细胞质和根尖抗坏血酸结合位点。Zn2+与顶抗坏血酸的两个羟基和一个组氨酸残基配位。生化分析表明，Fe3+与Zn2+竞争该结合位点。这些结果为还原剂促进铁离子吸收的机制提供了结构基础，并将促进基于结构的口服铁吸收改进剂的开发。Ganasen等人报道了人十二指肠细胞色素b及其与抗坏血酸和Zn2+的复合物的晶体结构。这项研究为还原剂如何促进口服铁的摄取提供了机制上的见解，并可能促进此类干预措施的发展。
Dietary iron absorption is regulated by duodenal cytochrome b (Dcytb), an integral membrane protein that catalyzes reduction of nonheme Fe3+ by electron transfer from ascorbate across the membrane. This step is essential to enable iron uptake by the divalent metal transporter. Here we report the crystallographic structures of human Dcytb and its complex with ascorbate and Zn2+. Each monomer of the homodimeric protein possesses cytoplasmic and apical heme groups, as well as cytoplasmic and apical ascorbate-binding sites located adjacent to each heme. Zn2+ coordinates to two hydroxyl groups of the apical ascorbate and to a histidine residue. Biochemical analysis indicates that Fe3+ competes with Zn2+ for this binding site. These results provide a structural basis for the mechanism by which Fe3+ uptake is promoted by reducing agents and should facilitate structure-based development of improved agents for absorption of orally administered iron. Ganasen et al. report the crystallographic structures of human duodenal cytochrome b and its complex with ascorbate and Zn2+. This study provides mechanistic insights into how reducing agents promote the uptake of orally administered iron and may facilitate the development of such interventions.
登录
查看更多内容
影响因子：
29
作者：
Drakesmith H;Nemeth E;Ganz T
通讯作者：
Ganz T
影响因子：
3
作者：
Balabin, Ilya A.;Hu, Xiangqian;Beratan, David N.
通讯作者：
Beratan, David N.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
8
作者：
HOLLAND, DR;HAUSRATH, AC;MATTHEWS, BW
通讯作者：
MATTHEWS, BW
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH