Coordination Chemistry of Microbial Iron Transport.
Coordination Chemistry of Microbial Iron Transport.
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DOI：
10.1021/acs.accounts.5b00301
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发表时间：
2015-09-15
影响因子：
18.3
通讯作者：
Sia AK
中科院分区：
文献类型：
--
作者：
Raymond KN;Allred BE;Sia AK
这个帐户的重点是配位化学的微生物铁螯合剂称为铁载体。最初的研究（20世纪70年代初）集中在铁载体的简单类似物上，包括异羟肟酸盐、儿茶酚盐或羟基羧酸盐配体。随后的工作越来越多地集中在铁载体的运输和微生物铁的运输。由于这些是通常由双齿配体组成的假八面体络合物，因此在金属中心处存在原则上独立于配体手性的手性。在许多情况下，已经表明发生络合物的手性识别。许多技术已被用来阐明在革兰氏阳性（单膜）和革兰氏阴性（双膜）细菌的铁吸收过程。这些包括使用放射性标记（配体，金属或两者），动力学惰性金属络合物和穆斯堡尔光谱。通常，铁载体识别和转运涉及识别铁-铁载体复合物的金属螯合物部分的受体。第二种机制，迄今为止不太常见，称为铁载体穿梭机制，涉及受体结合一个apo-siderophore。由于微生物相互竞争铁储存的主要方式之一是它们竞争铁载体复合物的强度，因此早期表征这些物种的溶液热力学变得很重要。由于铁载体的酸度变化很大，仅仅稳定常数并不能直接衡量结合的相对竞争强度。因此，比较pM值。与pH一样，pM是游离金属离子浓度的负对数的量度，通常在pH 7.4下计算，以及金属和配体的标准总浓度。铁载体的电子结构的表征已经做了很多工作，以帮助解释这些复合物的高稳定性。铁载体科学的一个新篇章已经出现了现在所谓的铁运载蛋白的特征。这些蛋白质最初被发现是人类先天免疫系统的蛋白质，它们结合铁和脱铁载体以阻止铁载体转运系统，从而阻止铁进入入侵的病原微生物。Siderocalins也可以在宿主的铁转运中发挥作用，特别是在胎儿发育的早期阶段。最后，据推测，不同物种中的铁运载蛋白的分子靶标不同，基于这些物种中最重要的细菌病原体的铁载体结构。
This Account focuses on the coordination chemistry of the microbial iron chelators called siderophores. The initial research (early 1970s) focused on simple analogs of siderophores, which included hydroxamate, catecholate, or hydroxycarboxylate ligands. The subsequent work increasingly focused on the transport of siderophores and their microbial iron transport. Since these are pseudo-octahedral complexes often composed of bidentate ligands, there is chirality at the metal center that in principle is independent of the ligand chirality. It has been shown in many cases that chiral recognition of the complex occurs. Many techniques have been used to elucidate the iron uptake processes in both Gram-positive (single membrane) and Gram-negative (double membrane) bacteria. These have included the use of radioactive labels (of ligand, metal, or both), kinetically inert metal complexes, and Mössbauer spectroscopy. In general, siderophore recognition and transport involves receptors that recognize the metal chelate portion of the iron–siderophore complex. A second, to date less commonly found, mechanism called the siderophore shuttle involves the receptor binding an apo-siderophore. Since one of the primary ways that microbes compete with each other for iron stores is the strength of their competing siderophore complexes, it became important early on to characterize the solution thermodynamics of these species. Since the acidity of siderophores varies significantly, just the stability constant does not give a direct measure of the relative competitive strength of binding. For this reason, the pM value is compared. The pM, like pH, is a measure of the negative log of the free metal ion concentration, typically calculated at pH 7.4, and standard total concentrations of metal and ligand. The characterization of the electronic structure of ferric siderophores has done much to help explain the high stability of these complexes. A new chapter in siderophore science has emerged with the characterization of what are now called siderocalins. Initially found as a protein of the human innate immune system, these proteins bind both ferric and apo-siderophores to inactivate the siderophore transport system and hence deny iron to an invading pathogenic microbe. Siderocalins also can play a role in iron transport of the host, particularly in the early stages of fetal development. Finally, it is speculated that the molecular targets of siderocalins in different species differ based on the siderophore structures of the most important bacterial pathogens of those species.