Jin Jinshan, Hsieh Ying-Hsin, Chaudhary Arpana S, Cui Jianmei, Houghton John E, Sui Sen-Fang, Wang Binghe, Tai Phang C
Department of Biology, Center for Biotechnology and Drug Design and Georgia State University, Atlanta, GA 30303, USA.
Department of Chemistry, Center for Biotechnology and Drug Design and Georgia State University, P.O. Box 3965, Atlanta, GA 30303, USA.
FEMS Microbiol Lett. 2018 Aug 1;365(15). doi: 10.1093/femsle/fny145.
Sec-dependent protein translocation is an essential process in bacteria. SecA is a key component of the translocation machinery and has multiple domains that interact with various ligands. SecA acts as an ATPase motor to drive the precursor protein/peptide through the SecYEG protein translocation channels. As SecA is unique to bacteria and there is no mammalian counterpart, it is an ideal target for the development of new antimicrobials. Several reviews detail the assays for ATPase and protein translocation, as well as the search for SecA inhibitors. Recent studies have shown that, in addition to the SecA-SecYEG translocation channels, there are SecA-only channels in the lipid bilayers, which function independently from the SecYEG machinery. This mini-review focuses on recent advances on the newly developed SecA inhibitors that allow the evaluation of their potential as antimicrobial agents, as well as a fundamental understanding of mechanisms of SecA function(s). These SecA inhibitors abrogate the effects of efflux pumps in both Gram-positive and Gram-negative bacteria. We also discuss recent findings that SecA binds to ribosomes and nascent peptides, which suggest other roles of SecA. A model for the multiple roles of SecA is presented.
依赖Sec的蛋白质转运是细菌中的一个重要过程。SecA是转运机制的关键组成部分，具有多个与各种配体相互作用的结构域。SecA作为一种ATP酶马达，驱动前体蛋白质/肽穿过SecYEG蛋白质转运通道。由于SecA是细菌特有的，且没有哺乳动物的对应物，因此它是开发新型抗菌药物的理想靶点。几篇综述详细介绍了ATP酶和蛋白质转运的检测方法，以及对SecA抑制剂的研究。最近的研究表明，除了SecA-SecYEG转运通道外，脂质双层中还存在仅含SecA的通道，其功能独立于SecYEG机制。这篇小型综述重点关注新开发的SecA抑制剂的最新进展，这些进展有助于评估它们作为抗菌剂的潜力，以及对SecA功能机制的基本理解。这些SecA抑制剂消除了革兰氏阳性菌和革兰氏阴性菌中外排泵的作用。我们还讨论了最近的发现，即SecA与核糖体和新生肽结合，这表明SecA还有其他作用。本文提出了一个SecA多重作用的模型。
