期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 294, 期 51, 页码 19523-19534出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA119.011018
关键词
membrane transport; X-ray crystallography; Escherichia coli (E; coli); protein structure; outer membrane; siderophore; bacterial outer membrane; ferric iron uptake (Fiu); iron acquisition; solute uptake; TonB-dependent transporter
资金
- Australian Research Council [FL130100038]
- National Health and Medical Research Council (NHMRC Program in Cellular Microbiology) [1092262]
- Australian Research Council [FL130100038] Funding Source: Australian Research Council
The ferric iron uptake (Fiu) transporter from Escherichia coli functions in the transport of iron?catecholate complexes across the bacterial outer membrane, providing the bacterium with iron, which is essential for growth. Recently it has become clear that Fiu also represents a liability for E. coli because its activity allows import of antimicrobial compounds that mimic catecholate. This inadvertent import suggests the potential utility of antimicrobial catechol siderophore mimetics in managing bacterial infections. However, to fully exploit these compounds, a detailed understanding of the mechanism of transport through Fiu and related transporters is required. To address this question, we determined the crystal structure of Fiu at 2.1?2.9 ? and analyzed its function in E. coli. Through analysis of the Fiuo crystal structure, in combination with in silico docking and mutagenesis, we provide insight into how Fiu and related transporters bind catecholate in a surface-exposed cavity. Moreover, through determination of the structure of Fiu in multiple crystal states, we revealed the presence of a large, selectively gated cavity in the interior of this transporter. This chamber is large enough to accommodate the Fiu substrate and may allow import of substrates via a two-step mechanism. This would avoid channel formation through the transporter and inadvertent import of toxic molecules. As Fiu and its homologs are the targets of substrate-mimicking antibiotics, these results may assist in the development of these compounds.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据