YidC as a potential antibiotic target
YidC as a potential antibiotic target
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DOI：
10.1016/j.bbamcr.2022.119403
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发表时间：
2022-11-30
影响因子：
5.1
通讯作者：
Kuhn，Andreas
中科院分区：
文献类型：
--
作者：
Dalbey，Ross E.;Kaushik，Sharbani;Kuhn，Andreas
膜插入酶是一种重要的细菌成分，在许多膜蛋白的生物形成过程中起折叠和插入作用。它是大肠杆菌内（细胞质）膜中的一种多跨越蛋白，通过疏水相互作用将其底物结合在“油腻滑片”中。底物的亲水部分在移入外周质之前短暂地定位于YidC的凹槽中。该凹槽位于膜的中心，两侧是油腻的滑动片，为阻断YidC插入酶功能的抑制剂提供了一个有希望的靶点。此外，由于油脂载片可与各种底物结合，因此也可为抑制分子提供结合位点。在这篇综述中，我们详细讨论了YidC的结构和机制，不仅与底物，而且与它的伙伴蛋白，SecYEG转位酶和SRP信号识别颗粒相互作用。深入了解底物与YidC催化槽的结合。最后，我们认为亲水性沟槽可能是药物结合的潜在位点，并且可以开发ydc靶向药物。
The membrane insertase YidC, is an essential bacterial component and functions in the folding and insertion of many membrane proteins during their biogenesis. It is a multispanning protein in the inner (cytoplasmic) membrane ofEscherichia colithat binds its substrates in the “greasy slide” through hydrophobic interaction. The hydrophilic part of the substrate transiently localizes in the groove of YidC before it is translocated into the periplasm. The groove, which is flanked by the greasy slide, is within the center of the membrane, and provides a promising target for inhibitors that would block the insertase function of YidC. In addition, since the greasy slide is available for the binding of various substrates, it could also provide a binding site for inhibitory molecules. In this review we discuss in detail the structure and the mechanism of how YidC interacts not only with its substrates, but also with its partner proteins, the SecYEG translocase and the SRP signal recognition particle. Insight into the substrate binding to the YidC catalytic groove is presented. We wind up the review with the idea that the hydrophilic groove would be a potential site for drug binding and the feasibility of YidC-targeted drug development.