STRUCTURAL PARAMETERS INVOLVED IN METAL RECOGNITION

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。生物体控制过渡金属离子的机制以及这些金属在细胞调节中的作用已成为金属生物化学研究的关键领域。生物系统需要特异性金属结合和反应，以避免蛋白质表达中金属之间的串扰，特定金属的摄取，以及将正确的金属掺入酶活性位点。关于金属蛋白如何识别、结合和响应所需金属离子的细节还没有很好地确定。对于过渡金属离子尤其如此，其中许多具有相似的电荷和离子半径。因此，它似乎有可能的配位几何形状和配体的偏好发挥重要作用，在区分过渡金属。该研究项目的总体目标是了解金属特异性结合的结构参数，以及参与金属贩运的金属蛋白中对特异性金属结合的相关蛋白质结构响应。为了实现这一目标，我们计划使用XAS来研究镍转运蛋白中镍位点的结构，包括：金属调节蛋白（NikR），金属转运蛋白（NikABCDE）和金属伴侣蛋白（HypA）--这些蛋白都参与了E. coli中的同源物，以及H.幽门。细菌的生存能力，包括人类病原体（如H。幽门螺杆菌），与所需金属（包括Ni）的获得有关，并且已经证明几种人类疾病是由金属贩运的中断引起的（例如，威尔逊和门克斯病的铜，遗传性血色素沉着症和其他遗传性铁超载疾病的铁）。此外，对金属运输所涉及的结构参数的详细了解可能会导致新的抗生素干扰细菌金属代谢，这通常是致病所必需的，以及开发对金属有抗性并可用于生物修复的植物

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The mechanisms by which organisms control transition metal ions and the roles of these metals in cellular regulation have emerged as key areas of investigation in metallobiochemistry. Specific metal binding and responses are required by biological systems in order to avoid cross-talk between metals in the expression of proteins, in the uptake of specific metals, and for the incorporation of the correct metal into enzyme active sites. The details of how the metalloproteins recognize, bind and respond to the presence of the requisite metal ion are not well established. This is particularly true for transition metal ions, many of which have similar charges and ionic radii. Thus, it seems likely that coordination geometry and ligand preferences play important roles in distinguishing transition metals. The overall objective of this research project is to understand the structural parameters that underlie metal-specific binding, and the related protein structural responses to specific metal binding, in metalloproteins involved in metal trafficking. Toward this goal, we plan to use XAS to examine the structures of Ni sites in nickel trafficking proteins including: a metalloregulator (NikR), a metallotransporter (NikABCDE) and a metallochaperone (HypA)--proteins all involved in nickel trafficking in E. coli, and their homologs in H. pylori. The viability of bacteria, including human pathogens (like H. pylori), is linked to the acquisition of required metals (including Ni), and several human diseases have been shown to result from a breakdown in metal trafficking (e.g., Wilson's and Menkes¿¿ diseases for copper, genetic hemochromatosis and other hereditary iron overload disorders for iron). In addition, a detailed understanding of the structural parameters involved in metal-trafficking may lead to new antibiotics that interfere with bacterial metal metabolism, which is frequently essential for pathogenesis, and the development of plants that are resistant to metals and useful in bioremed