STRUCTURAL PARAMETERS INVOLVED IN METAL RECOGNITION

金属识别涉及的结构参数

• 批准号: 7954256
• 负责人: MICHAEL J MARONEY
• 金额: $ 0.66万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954256
• 关键词: Active Sites; Amino Acids; Antibiotics; Area; Bacteria; Binding; 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; Radial; Research; Research Personnel; Research Project Grants; Resources; Role; Site; Source; Structural Protein; Structure; Transition Elements; United States National Institutes of Health; biological systems; cell growth regulation; design; human disease; metal metabolism; pathogen; preference; protein expression; protein transport; response; structural biology; synchrotron radiation; 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 生物体控制过渡金属离子和这些金属在细胞调节中的作用的机制已成为金属异生化学研究的关键领域。 生物系统需要特定的金属结合和反应，以避免金属在蛋白质表达，特定金属的摄取以及将正确的金属掺入酶活性位点中的金属之间的串扰。 金属蛋白如何识别，结合和应对必要金属离子的存在的细节尚未得到充分确定。 对于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，似乎有可能在区分过渡金属方面的协调几何形状和配体偏好（至少在氨基酸提供的配体中）起着重要作用。该研究项目的总体目的是了解金属特异性结合的结构参数，以及与金属运输的金属蛋白中有关特定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检查镍运输蛋白中的NI位点的结构，包括：金属糖浆（NIKR），金属转运蛋白（Nikabcde）和金属蛋白（HYPA）（HYPA） - 蛋白质 - 蛋白质 - 蛋白质均涉及E. Coli中的镍和其H. pylori in h. pylori。 包括人类病原体在内的细菌的活力与获得所需金属的获取（包括NI）有关，并且已经证明，金属贩运的分解（例如Wilson's and Menkes是铜的疾病？铜，遗传性血糖症和其他遗传性铁过载疾病）。此外，对贩运金属贩运的结构参数的详细理解可能会导致设计新的抗生素，从而干扰细菌金属代谢。