Dynamic Properties that Enhance Enzyme Function

增强酶功能的动态特性

• 批准号: 8052862
• 负责人: Sidney M. Hecht
• 金额: $ 31.19万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8052862
• 关键词: Acids; Active Sites; Address; Allosteric Regulation; Amino Acids; Antineoplastic Agents; Behavior; Binding; Biochemical Reaction; Catalysis; Characteristics; Chemicals; Coupled; Coupling; Development; Dihydrofolate Reductase; Distant; Environment; Enzymes; Event; Evolution; Fluorescence Spectroscopy; Fluorescent Probes; Fostering; Freedom; Frequencies; Goals; Investigation; Kinetics; Knowledge; Label; Laboratories; Lead; Maps; Mediating; Methodology; Methods; Modification; Motion; NMR Spectroscopy; Nature; Physiological; Play; Post-Translational Protein Processing; Process; Property; Protein Dynamics; Protein Subunits; Proteins; Publishing; Reaction; Research; Resolution; Role; Side; Site; Solutions; Solvents; Structure; System; Tertiary Protein Structure; Time; Vertebral column; Work; X-Ray Crystallography; antimicrobial drug; base; cofactor; design; drug discovery; enzyme mechanism; enzyme substrate complex; flexibility; fluorophore; improved; insight; novel; operation; protein folding; protein function; protein structure; protein structure function; public health relevance; research and development; single molecule; three dimensional structure; tool

DESCRIPTION (provided by applicant): The long term goals of this research include the development of methodology to permit the folding, flexibility and dynamics of protein structure to be interrogated, and the development and use of fluorescent probes in novel ways to enhance our understanding of protein structure, dynamics and function. During the five years of proposed research, the focus of efforts will be on study of the mechanism of modified DHFRs through steady state, pre-steady state and single molecule kinetic studies. Fluorescence spectroscopy will be used to study the protein conformational changes and their association with the key steps in DHFR catalysis. PUBLIC HEALTH RELEVANCE: The present project is aimed at describing and quantifying the particular sequence, structural and dynamic properties that operate to enhance enzymatic catalysis. The proposed studies will provide important insights into enzyme function and will foster protein design and drug discovery efforts. The enzyme DHFR, which is the target of important antineoplastic and antimicrobial drugs, will be the focus of our efforts.

描述（由申请人提供）：本研究的长期目标包括开发允许研究蛋白质结构的折叠、灵活性和动态的方法，以及以新的方式开发和使用荧光探针以增强我们对蛋白质结构、动态和功能的理解。在拟议的五年研究中，工作重点将是通过稳态、前稳态和单分子动力学研究修饰 DHFR 的机制。荧光光谱将用于研究蛋白质构象变化及其与 DHFR 催化关键步骤的关联。 公共健康相关性：本项目旨在描述和量化增强酶催化作用的特定序列、结构和动态特性。拟议的研究将为酶功能提供重要见解，并将促进蛋白质设计和药物发现工作。 DHFR酶是重要的抗肿瘤和抗菌药物的靶标，将是我们努力的重点。