STRUCTURAL PARAMETERS INVOLVED IN METAL RECOGNITION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 生物控制过渡金属离子的机制以及这些金属在细胞调控中的作用已成为矿物生物化学中的关键研究领域。生物系统需要特定的金属结合和反应，以避免金属之间在蛋白质表达、特定金属的吸收以及将正确的金属掺入酶活性部位的串扰。关于金属蛋白如何识别、结合和响应所需的金属离子的细节还没有很好地确定。过渡金属离子尤其如此，其中许多离子具有相似的电荷和离子半径。因此，配位几何构型和配体偏好(至少在氨基酸提供的配体中)似乎在区分过渡金属方面起着重要作用。这个研究项目的总体目标是了解参与金属运输的金属蛋白中构成金属特异性结合的结构参数，以及相关的蛋白质结构对特定金属结合的反应。为此，我们计划使用XAS来检测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)和金属配位转运蛋白(HYPA)--这些蛋白都与大肠杆菌中的镍运输有关，以及它们在幽门螺杆菌中的同源物。细菌的生存能力，包括人类病原体，与获得所需的金属(包括镍)有关，已证明几种人类疾病是由金属贩运的崩溃引起的(例如，威尔逊病和门克斯病？铜病、遗传性血色素沉着症和其他遗传性铁过载疾病(铁的遗传性疾病)。此外，对参与金属运输的结构参数的详细了解可能会导致设计出干扰细菌金属代谢的新抗生素。

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 metals into enzyme active sites. The details of how the metalloproteins recognize, bind and respond to the presence of the requisite metal ions is 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 (at least among the ligands provided by amino acids) 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, 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 the design of new antibiotics that interfere with bacterial metal metabolism.