The structure and function analysis of MATE transporter in Mammal.

哺乳动物MATE转运蛋白的结构和功能分析。

• 批准号: 18590057
• 负责人: OTSUKA Masato
• 金额: $ 2.53万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590057/
• 关键词: Multidrug; Transporter; organic cation; Multidrug transporter; organic cation transporter; kidney; MATE; Organic cation transport

Human multidrug and toxic compound extrusion 1 (hMATE1) is an electroneutral H(+)/organic cation exchanger responsible for the final excretion step of structurally unrelated toxic organic cations in kidney and liver. To elucidate the molecular basis of the substrate recognition by hMATE1, we substituted the glutamate residues Glu273, Glu278, Glu300, and Glu389, which are conserved in the transmembrane regions, for alanine or aspartate and examined the transport activities of the resulting mutant proteins using tetraethylammonium (TEA) and cimetidine as substrates after expression in human embryonic kidney 293 (HEK-293) cells. All of these mutants except Glu273Ala were fully expressed and present in the plasma membrane of the HEK-293 cells. TEA transport activity in the mutant Glu278A1a was completely absent. Both Glu300Ala and Glu389Ala and all aspartate mutants exhibited significantly decreased activity. Glu273Asp showed higher affinity for cimetidine, whereas it has reduced affinity to TEA. Glu278Asp showed decreased affinity to cimetidine. Both Glu300Asp and Glu389Asp had lowered affinity to TEA, whereas the affinity of Glu389Asp to cimetidine was fourfold higher than that of the wild-type transporter with about a fourfold decrease in V(max) value. Both Glu273Asp and Glu300Asp had altered pH dependence for TEA uptake. These results suggest that all of these glutamate residues are involved in binding and/or transport of TEA and cimetidine but that their individual roles are different.

人类多药和有毒化合物挤出1（Hmate1）是负责肾脏和肝脏结构无关的有毒有机阳离子的最终排泄步骤的有机阳离子交换器。为了阐明HMATE 1的底物识别的分子基础，我们用谷氨酸残基GLU273，GLU278，GLU300和GLU389代替，在跨膜区域中保守，在跨膜区域中保守，用于丙氨酸或天冬氨酸，并使用结果和天冬氨酸进行了促成的the素（促成the）的转运（在人类胚胎肾脏293（HEK-293）细胞中的表达。除GLU273ALA以外的所有这些突变体都完全表达，并存在于HEK-293细胞的质膜中。完全不存在突变体GLU278A1A中的茶传输活性。 GLU300ALA和GLU389ALA以及所有天冬氨酸突变体的活性显着降低。 GLU273ASP显示出对Cimetidine的较高亲和力，而对茶的亲和力降低了。 GLU278ASP显示对甲氧胺的亲和力降低。 GLU300ASP和GLU389ASP都降低了对茶的亲和力，而Glu389ASP与Cimetidine的亲和力比野生型转运蛋白的亲和力高四倍，而V（MAX）值的降低约为四倍。 GLU273ASP和GLU300ASP都改变了pH依赖性茶的摄取。这些结果表明，所有这些谷氨酸残基都参与茶和甲己丁的结合和/或运输，但它们的各个角色都不同。

项目成果

A novel variant of mouse MATE-1 H+/organic cation antiporter with a long hydrophobic tail

具有长疏水尾的小鼠 MATE-1 H /有机阳离子逆向转运蛋白的新变体

• 发表时间: 2008
• 期刊: Arch. Biochem. Biophys. 469
• 作者: Kobara;A.;Hiasa;N.;Matsumoto;T.;Otsuka;M.;Omote;H.;and Moriyama;Y.
• 通讯作者: Y.

The MATE proteins as fundamental transporters of metabolic and xenobiotic organic cations

• DOI: 10.1016/j.tips.2006.09.001
• 发表时间: 2006-11-01
• 期刊: TRENDS IN PHARMACOLOGICAL SCIENCES
• 影响因子: 13.8
• 作者: Omote, Hiroshi;Hiasa, Miki;Moriyama, Yoshinori
• 通讯作者: Moriyama, Yoshinori

哺乳動物における新規薬物排出輸送体財MATEの構造と機能及び相互作用

哺乳动物中新型药物外排转运蛋白 MATE 的结构、功能和相互作用

• 发表时间: 2007
• 作者: 林 秀敏;ら;Katsuki H (第一著者);大塚 正人
• 通讯作者: 大塚 正人

Identification of a vesicular nucleotide transporter

• DOI: 10.1073/pnas.0800141105
• 发表时间: 2008-04-15
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Sawada, Keisuke;Echigo, Noriko;Moriyama, Yoshinori
• 通讯作者: Moriyama, Yoshinori

The structure and fimction analysis of MATE transporter in Mammal

哺乳动物MATE转运蛋白的结构和功能分析

• 发表时间: 2007
• 作者: M.;Otsuka
• 通讯作者: Otsuka