Complex Metallocluster Structure and Assembly

复杂金属簇结构和组装

• 批准号: 7736814
• 负责人: CATHERINE L DRENNAN
• 金额: $ 27.69万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-02 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7736814
• 关键词: Acetyl Coenzyme A; Affinity; Area; Binding; Binding Sites; Biogenesis; Biological Process; Biology; Biomimetics; Carbon; Carbon Dioxide; Carbon Monoxide; Carbon monoxide dehydrogenase; Chemicals; Chemistry; Cobalamin; Collaborations; Complex; Computing Methodologies; Corrinoids; Crystallography; DNA; Data; Environment; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Enzymes; Escherichia coli; Exposure to; Folate; Funding; Goals; Helicobacter pylori; Homeostasis; Human; Ions; Iron; Iron-Sulfur Proteins; Life; Ligands; Location; Maps; Metabolism; Metals; Methane; Methyltransferase; Modeling; Mutagenesis; Nickel; Pathway interactions; Phase; Potassium; Process; Production; Protein Methyltransferases; Protein Region; Proteins; Reaction; Regulation; Research; Site; Specificity; Structure; Sulfur; System; Trace Elements; Trace metal; Work; X-Ray Crystallography; catalyst; cell growth regulation; cysteine desulfurase; design; electron density; fascinate; genetic regulatory protein; interest; metalloenzyme; multiple myeloma M Protein; mutant; novel; oxidation; pathogen; public health relevance; repaired; sample fixation; tool; uptake

DESCRIPTION (provided by applicant): Metal ions in biology allow for an expanded chemical repertoire; the local protein environment and metal coordination sphere act synergistically to confer unique reactivity. It is therefore not surprising that the reactions catalyzed by metalloenzymes are chemically challenging and essential for life. We use X-ray crystallography and computation to study the structure and mechanism of complex metallocofactors. Our findings have applications for the synthesis of biomimetic catalysts and in the design of enzyme inhibitors. In addition to interrogating the mechanisms of metalloenzymes, it is important to investigate the cellular regulation of trace mineral levels required for metallocenter assembly, as well as to study the assembly process itself. This proposal focuses on nickel and iron-sulfur containing proteins and their metallochaperones, as well as the regulation of nickel uptake and iron-sulfur cluster assembly. PUBLIC HEALTH RELEVANCE: The proposed research uses X-ray crystallography and computation as the chief tools to investigate nickel, iron-sulfur and corrinoid containing proteins, with a focus on proteins involved in one-carbon metabolism. Our goals are to explore the mechanism and assembly of complex metallocofactors, as well as the cellular regulation of nickel uptake and iron-sulfur cluster biogenesis.

描述（由申请人提供）：生物学中的金属离子允许扩大化学曲目；局部蛋白质环境和金属配位球协同作用以赋予独特的反应性。因此，毫不奇怪的是，金属酶催化的反应在化学上具有挑战性，对生命至关重要。我们使用X射线晶体学和计算来研究复杂的金属生产者的结构和机理。我们的发现有用于合成仿生催化剂和酶抑制剂设计的应用。除了审问金属酶的机制外，重要的是研究金属中心装配所需的痕量矿物水平的细胞调节以及研究组装过程本身。该提案的重点是含有蛋白质及其金属蛋白的镍和铁硫，以及镍摄取和铁硫簇组装的调节。公共卫生相关性：拟议的研究使用X射线晶体学和计算作为研究镍，铁硫和含有蛋白质的镍，含蛋白的主要工具，重点是涉及参与单碳代谢的蛋白质。我们的目标是探索复杂的金属效应器的机制和组装，以及镍摄取和铁硫簇生物发生的细胞调节。