Review Article

ATP结合盒式出口商:结构和机制,重点是P-糖蛋白和MRP1

卷 26, 期 7, 2019

页: [1062 - 1078] 页: 17

弟呕挨: 10.2174/0929867324666171012105143

价格: $65

摘要

背景:属于ATP结合盒超家族的蛋白质包括介导底物从细胞外排的转运蛋白。在这些出口商中,P-糖蛋白和MRP1参与癌症多药耐药性,内皮和异生素的保护,药物药代动力学的确定以及各种疾病的病理生理学。 目的:回顾有关ATP结合盒出口商的可用信息,重点是Pglycoprotein,MRP1和相关蛋白。我们描述了这些转运蛋白在健康和疾病中的组织定位和功能,并讨论了底物转运的机制。我们还将最近的结构信息与出口商的功能联系起来,并讨论其分子机制的细节,重点是核苷酸结合域。 方法:评估所选出版物中ATP结合盒蛋白的结构和功能。 结论:出口商的核苷酸结合域侧的构象变化改变了内部和外部之间的底物结合口袋的可接近性,其与基质外排偶联。然而,对驱动替代可及性的核苷酸结合域侧的变化的大小和性质没有一致意见。比较Pglycoprotein和MRP1的结构有助于解释底物选择性的差异和多特异性的基础。 P-糖蛋白底物是疏水性和/或弱碱性,并且多特异性通过具有少量酸性斑块的柔性疏水性多结合位点来解释。 MRP1底物主要是有机酸,其多特异性是由于单个二分结合位点是柔性的并且显示出正电荷。

关键词: ATP结合盒,多药耐药性,核苷酸结合结构域,二聚体,水解,Pglycoprotein,MRP1,ABCB,ABCC。

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