Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA.
Nat Prod Rep. 2016 Oct 26;33(11):1255-1267. doi: 10.1039/c6np00006a.
Covering: 2009 to mid 2016Multidrug transporters are common and prevalent in all orders of life, having diverse functions from the removal of toxins, resistance to cytotoxins, and the transport of specific eluents. In addition, multidrug transporters pose a significant threat to modern medicine. Able to transport structurally diverse small molecule drugs, these transporters are implicated in antibiotic resistant strains of bacteria, as well as chemotherapeutic-resistance cancer cells. Although important in such resistance, a relatively small number of multidrug transporters have been structurally characterized, primarily due to the difficulty in purifying and crystallizing active membrane proteins and protein complexes. This review will cover recent structural breakthroughs in the past six years that have led to increased knowledge of the mechanisms of multidrug transporter chemistry, and the role of these transporters in exporting secondary metabolites.
2009 年至 2016 年年中
多药转运蛋白在所有生命形式中都很常见且普遍存在,具有从去除毒素、抵抗细胞毒素以及运输特定洗脱液等多种功能。此外,多药转运蛋白对现代医学构成了重大威胁。这些转运蛋白能够运输结构多样的小分子药物,与细菌的抗生素耐药株以及化疗耐药癌细胞有关。尽管在这种耐药性中很重要,但只有相对较少的多药转运蛋白的结构得到了表征,主要是由于纯化和结晶活性膜蛋白和蛋白复合物的困难。这篇综述将涵盖过去六年中在结构上的突破,这些突破使人们对多药转运蛋白化学机制以及这些转运蛋白在排出次生代谢物中的作用有了更多的了解。