A macrocyclic peptide that serves as a cocrystallization ligand and inhibits the function of a MATE family transporter.
A macrocyclic peptide that serves as a cocrystallization ligand and inhibits the function of a MATE family transporter.
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DOI：
10.3390/molecules180910514
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发表时间：
2013-08-30
期刊：
影响因子：
--
通讯作者：
Suga H
中科院分区：
文献类型：
--
作者：
Hipolito CJ;Tanaka Y;Katoh T;Nureki O;Suga H
随机非标准肽整合发现（Random Non-Standard Peptide Integrated Discovery，RaPID）系统是一种有效的方法，可以从天然产物中发现抑制蛋白质功能的大环肽。我们最近报道了三个大环肽，结合激烈火球菌多药和毒性化合物外排转运蛋白（PfMATE），并抑制运输功能。此外，这些大环肽被成功地用作硒代蛋氨酸标记的PfMATE的共结晶配体。在这份报告中，我们公开了RaPID选择策略的细节，该策略导致了这三种大环肽的鉴定以及第四种大环肽MaD 8的鉴定，MaD 8在本文中专门讨论。MaD 8被发现结合在PfMATE细胞外侧的裂缝内，并阻断了有机小分子被挤出的路径。溴化乙锭外排试验的结果证实了MaD 8的外排抑制活性，其行为与先前报道的MaD 5相似。
The random non-standard peptide integrated discovery (RaPID) system has proven to be a powerful approach to discover de novo natural product-like macrocyclic peptides that inhibit protein functions. We have recently reported three macrocyclic peptides that bind to Pyrococcus furiosus multidrug and toxic compound extrusion (PfMATE) transporter and inhibit the transport function. Moreover, these macrocyclic peptides were successfully employed as cocrystallization ligands of selenomethionine-labeled PfMATE. In this report, we disclose the details of the RaPID selection strategy that led to the identification of these three macrocyclic peptides as well as a fourth macrocyclic peptide, MaD8, which is exclusively discussed in this article. MaD8 was found to bind within the cleft of PfMATE’s extracellular side and blocked the path of organic small molecules being extruded. The results of an ethidium bromide efflux assay confirmed the efflux inhibitory activity of MaD8, whose behavior was similar to that of previously reported MaD5.
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DOI：
10.1073/pnas.1219901110
发表时间：
2013-02-05
影响因子：
11.1
作者：
Lu, Min;Symersky, Jindrich;Koide, Shohei
通讯作者：
Koide, Shohei
影响因子：
3.5
作者：
Nemoto, N;MiyamotoSato, E;Yanagawa, H
通讯作者：
Yanagawa, H
影响因子：
13.6
作者：
Masuda, Satohiro;Terada, Tomohiro;Inui, Ken-ichi
通讯作者：
Inui, Ken-ichi
影响因子：
5.7
作者：
Hunte, C;Koepke, J;Michel, H
通讯作者：
Michel, H
影响因子：
6.8
作者：
Cherezov, Vadim
通讯作者：
Cherezov, Vadim