STRUCTURAL PARAMETERS INVOLVED IN METAL RECOGNITION

金属识别涉及的结构参数

• 批准号: 7721904
• 负责人: MICHAEL J MARONEY
• 金额: $ 0.73万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721904
• 关键词: Active Sites; Amino Acids; Antibiotics; Area; Bacteria; Binding; Biological; Charge; Computer Retrieval of Information on Scientific Projects Database; Copper; Enzymes; Escherichia coli; Funding; Genetic; Goals; Grant; Helicobacter pylori; Hemochromatosis; Homologous Gene; Human; Inherited; Institution; Investigation; Ions; Iron Metabolism Disorders; Iron Overload; Lead; Ligands; Link; Menkes Kinky Hair Syndrome; Metalloproteins; Metals; Nickel; Organism; Play; Proteins; Research; Research Personnel; Research Project Grants; Resources; Role; Site; Source; Structural Protein; Structure; System; Transition Elements; United States National Institutes of Health; cell growth regulation; design; human disease; intracellular protein transport; metal metabolism; pathogen; preference; protein expression; protein transport; radius bone structure; response; trafficking; uptake

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。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 研究中心，而研究中心不一定是研究者所在的机构。 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，似乎可能的是，配位几何形状和配体偏好（至少在由氨基酸提供的配体中）在区分过渡金属中起重要作用。本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对特异性金属结合的相关蛋白质结构反应。 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.幽门螺杆菌。 包括人类病原体在内的细菌的生存能力与所需金属（包括Ni）的获得有关，并且已经表明，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？用于铜的疾病、遗传性血色病和用于铁的其它遗传性铁过载病症）。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设计新的抗生素，干扰细菌金属代谢。