CAREER: Structure, Mechanism, and Selectivity of Microbial Ferrous Iron Transport

通过这一奖项，化学部生命过程化学计划资助巴尔的摩县马里兰大学的Aaron T.Smith博士研究铁在细菌中的运输。铁对地球上几乎所有生物的生存都是必不可少的，包括那些只由一个细胞和人类组成的生物。虽然一些铁(Fe+3)的生物获取已被很好地研究，但对其他铁物种(Fe+2)的获取却知之甚少。这项研究试图了解Fe+2是如何通过细菌的膜运输的，这些细菌存在于人体内，影响人类健康。这项研究的结果可能有助于科学家设计控制细菌感染的新型抗生素。进行这项研究的研究生学习如何处理和研究对空气敏感的金属蛋白，以便准确定位原子级别的铁运输细节。这个项目通过向一年级和二年级的本科生介绍生物无机化学，在化学课程中发展生物无机化学实验，以及设计和实施专门的高级生物无机化学课程，增加了该领域中未被充分代表的个人的多样性和包容性。本研究的总体目标是阐明三蛋白系统FeO调节Fe(II)跨细菌膜运输的机制。这项研究的一个重要方面是对重组蛋白的研究，包括完整的FeoB，它是一种复杂的膜蛋白，是FeO系统的中心参与者。此外，本研究还利用FeoB可能的相互作用伙伴--重组的、可溶的FeoA和FeoC来确定Fe(II)转运的调控。本研究利用光谱学(电子吸收、圆二色谱、EPR和X射线吸收)、生物化学和结构生物学(X射线结晶学)方法来确定电子结构、三维结构和这一过程的动力学。这项研究为控制铁运输的小分子设计提供了目标，这是细菌必不可少的过程。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Aaron T. Smith of the University of Maryland, Baltimore County to study the transport of iron (Fe) in bacteria. Iron is essential for the survival of almost all organisms on the planet, including those organisms made of only one cell and humans. While the biological acquisition of some iron (Fe+3) is well studied, the acquisition of other iron species (Fe+2) is poorly understood. This research seeks to understand how Fe+2 is transported across the membrane of bacteria which are present in the human body and affect human health. The results of this research could help scientists design novel antibiotics that control bacterial infections. The graduate students who conduct this research learn how to handle and study metalloproteins that are sensitive to air in order to pinpoint atomic-level details of iron transport. This project increases diversity and inclusion of underrepresented individuals within the field through an introduction of freshman and sophomore undergraduates to bioinorganic chemistry, the development of bioinorganic laboratory experiments in the chemistry curriculum, and the design and implementation of a dedicated upper-level bioinorganic chemistry course.The overarching goal of this research is to elucidate the mechanism by which the three-protein system Feo mediates the transport of Fe(II) across the membrane of bacteria. An important aspect of this research is the focus on recombinant proteins, including the intact FeoB, which is a complex membrane protein and the central player of the Feo system. Moreover, this research uses recombinant, soluble FeoA and FeoC, putative interaction partners of FeoB, to determine the regulation of Fe(II) transport. This research makes use of spectroscopy (electron absorption, circular dichroism, EPR, and X-ray absorption), biochemistry, and structural biology (X-ray crystallography) methods to determine electronic structure, three-dimensional structure, and the dynamics of this process. This research provides targets for the design of small molecules to control iron transport, a process essential for bacteria.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.