Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
Biometals. 2010 Aug;23(4):601-11. doi: 10.1007/s10534-010-9361-x. Epub 2010 Jul 2.
Siderophores are biosynthetically produced and secreted by many bacteria, yeasts, fungi and plants, to scavenge for ferric iron (Fe(3+)). They are selective iron-chelators that have an extremely high affinity for binding this trivalent metal ion. The ferric ion is poorly soluble but it is the form of iron that is predominantly found in oxygenated environments. Siderophore uptake in bacteria has been extensively studied and over the last decade, detailed structural information for many of the proteins that are involved in their transport has become available. Specifically, numerous crystal structures for outer membrane siderophore transporters, as well as for soluble periplasmic siderophore-binding proteins, have been reported. Moreover, unique siderophore-binding proteins have recently been serendipitously discovered in humans, and the structures of some of their siderophore-complexes have been characterized. The binding pockets for different ferric-siderophores in these proteins have been described in great molecular detail. In addition to highlighting this structural information, in this review paper we will also briefly discuss the relevant chemical properties of iron, and provide a perspective on our current understanding of the human and bacterial iron uptake pathways. Potential clinical uses of siderophores will also be discussed. The emerging overall picture is that iron metabolism plays an extremely important role during bacterial infections. Because levels of free ferric iron in biological systems are always extremely low, there is serious competition for iron and for ferric-siderophores between pathogenic bacteria and the human or animal host.
铁载体是许多细菌、酵母、真菌和植物生物合成并分泌的，用于掠取三价铁（Fe(3+)）。它们是选择性的铁螯合剂，对结合这种三价金属离子具有极高的亲和力。三价铁离子的溶解度较低，但它是在氧化环境中主要存在的铁的形式。细菌中铁载体的摄取已经得到了广泛的研究，在过去的十年中，涉及它们运输的许多蛋白质的详细结构信息已经可用。具体来说，已经报道了许多外膜铁载体转运蛋白以及可溶周质腔铁载体结合蛋白的晶体结构。此外，最近在人类中偶然发现了独特的铁载体结合蛋白，并且已经对其一些铁载体复合物的结构进行了表征。这些蛋白质中不同的三价铁-铁载体结合口袋已经在很大的分子细节上进行了描述。除了突出这些结构信息外，在这篇综述文章中，我们还将简要讨论铁的相关化学性质，并提供对人类和细菌铁摄取途径的当前理解的视角。还将讨论铁载体的潜在临床用途。总体情况是，铁代谢在细菌感染过程中起着极其重要的作用。由于生物系统中游离三价铁的水平总是极低，因此致病菌和人类或动物宿主之间存在严重的铁和三价铁载体竞争。
