基于结构的观点看 ABC 转运蛋白与多药耐药的关系。

Department of Pharmaceutical Sciences, University of Vienna, 1140 Vienna, Austria.

Molecules. 2023 Jan 4;28(2):495. doi: 10.3390/molecules28020495.

The discovery of the first ATP-binding cassette (ABC) transporter, whose overexpression in cancer cells is responsible for exporting anticancer drugs out of tumor cells, initiated enormous efforts to overcome tumor cell multidrug resistance (MDR) by inhibition of ABC-transporter. Because of its many physiological functions, diverse studies have been conducted on the mechanism, function and regulation of this important group of transmembrane transport proteins. In this review, we will focus on the structural aspects of this transporter superfamily. Since the resolution revolution of electron microscope, experimentally solved structures increased rapidly. A summary of the structures available and an overview of recent structure-based studies are provided. More specifically, the artificial intelligence (AI)-based predictions from AlphaFold-2 will be discussed.

首个三磷酸腺苷结合盒（ABC）转运蛋白的发现，其在癌细胞中的过度表达导致抗癌药物从肿瘤细胞中排出，这促使人们做出巨大努力来通过抑制 ABC 转运蛋白来克服肿瘤细胞多药耐药性（MDR）。由于其许多生理功能，人们对这组重要的跨膜转运蛋白的机制、功能和调节进行了广泛的研究。在这篇综述中，我们将重点介绍该转运蛋白超家族的结构方面。自电子显微镜分辨率革命以来，实验解决的结构迅速增加。本文提供了现有结构的概述和最近基于结构的研究综述。更具体地说，将讨论基于人工智能（AI）的 AlphaFold-2 的预测。