Chitsaz Mohsen, Brown Melissa H
School of Biological Sciences, Flinders University, Adelaide, South Australia, Australia.
School of Biological Sciences, Flinders University, Adelaide, South Australia, Australia
Essays Biochem. 2017 Mar 3;61(1):127-139. doi: 10.1042/EBC20160064. Print 2017 Feb 28.
Antimicrobial resistance is a current major challenge in chemotherapy and infection control. The ability of bacterial and eukaryotic cells to recognize and pump toxic compounds from within the cell to the environment before they reach their targets is one of the important mechanisms contributing to this phenomenon. Drug efflux pumps are membrane transport proteins that require energy to export substrates and can be selective for a specific drug or poly-specific that can export multiple structurally diverse drug compounds. These proteins can be classified into seven groups based on protein sequence homology, energy source and overall structure. Extensive studies on efflux proteins have resulted in a wealth of knowledge that has made possible in-depth understanding of the structures and mechanisms of action, substrate profiles, regulation and possible inhibition of many clinically important efflux pumps. This review focuses on describing known families of drug efflux pumps using examples that are well characterized structurally and/or biochemically.
抗菌耐药性是当前化疗和感染控制中的一个主要挑战。细菌和真核细胞在有毒化合物到达其靶点之前识别并将其从细胞内泵送到细胞外环境的能力是导致这一现象的重要机制之一。药物外排泵是一种膜转运蛋白,需要能量来输出底物,并且可以对特定药物具有选择性,或者是多特异性的,可以输出多种结构不同的药物化合物。根据蛋白质序列同源性、能量来源和整体结构,这些蛋白质可分为七组。对外排蛋白的广泛研究产生了丰富的知识,使得深入了解许多临床重要外排泵的结构、作用机制、底物谱、调控和可能的抑制成为可能。本综述重点描述已知的药物外排泵家族,并列举结构和/或生化特征明确的实例。